Version: 8.0.0Date: Tue Jan 28 2025
HTP Dataset Index Anatomical Expression: hepatobiliary system
Expression data from lenses triply deficient for E2F1, E2F2, and E2F3 transcription factors
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-16533, GEO:GSE16533
Tags: WT vs. mutant, developmental stage, genotype
Summary: The E2F family consists of transcriptional repressors and activators that control cell proliferation. In the classic paradigm of cell cycle regulation, the three activators, E2F1, E2F2 and E2F3, are invariably depicted as the final components of a CDK/Rb signaling cascade that executes the transcriptional program necessary to commit cells to enter S phase. Unexpectedly, we find through analysis of Affymetrix expression array data that mature lens epithelial cells deficient for E2F1-3 fail to repress cell cycle-regulated genes (and other targets of E2F) and that this corresponds with subsequent apoptosis and cellular collapse in the lens. Murine lenses were collected at two stages of development for RNA extraction and hybridization on Affymetrix microarrays. Our aim was to determine key events that lead to cellular collapse of lenses triply deficient for E2F1, E2F2, and E2F3 in neonates.
Symbol: Expression data from lenses triply deficient for E2F1, E2F2, and E2F3 transcription factors
Estrogen receptor-dependent attenuation of hypoxia-induced changes in the lung genome of pulmonary hypertension rats
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE85618
Tags: unclassified
Summary: 17β-estradiol (E2) exerts complex and context-dependent effects in pulmonary hypertension. In hypoxia-induced pulmonary hypertension (HPH), E2 attenuates lung vascular remodeling through estrogen receptor (ER)-dependent effects; however, ER target genes in the hypoxic lung remain unknown. In order to identify the genome regulated by the E2-ER axis in the hypoxic lung, we performed a microarray analysis in lungs from HPH rats treated with E2 (75 mcg/kg/d) ± ER-antagonist ICI182,780 (3 mg/kg/d). Untreated HPH rats and normoxic rats served as controls. Using a false discovery rate of 10%, we identified a significantly differentially regulated genome in E2-treated vs. untreated hypoxia rats. Genes most up-regulated by E2 encoded matrix metalloproteinase 8, S100 calcium binding protein A8, and IgA Fc receptor; genes most down-regulated by E2 encoded olfactory receptor 63, secreted frizzled-related protein 2, and thrombospondin 2. Several genes affected by E2 changed in the opposite direction after ICI182,780 co-treatment, indicating an ER-regulated genome in HPH lungs. The bone morphogenetic protein antagonist Grem1 (gremlin 1) was up-regulated by hypoxia, but found to be among the most down-regulated genes after E2 treatment. Gremlin 1 protein was reduced in E2-treated vs. untreated hypoxic animals, and ER-blockade abolished the inhibitory effect of E2 on Grem1 mRNA and protein. In conclusion, E2 ER-dependently regulates several genes involved in proliferative and inflammatory processes during hypoxia. Gremlin 1 is a novel target of the E2-ER axis in HPH. Understanding the mechanisms of E2 gene regulation in HPH may allow for selectively harnessing beneficial transcriptional activities of E2 for therapeutic purposes.
To elucidate the role of estradiol- 17ß (E2) in the regulation of corpus luteum function
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE41735
Tags: unclassified
Summary: Corpus luteum (CL) is a transient endocrine tissue formed from the remnants of the ovarian follicle after ovulation. In response to gonadotropin surge, the ovulating follicle undergoes dramatic changes in expression of genes and differentiation of follicular cells into luteal cells. In several species, of the several genes that are down- regulated post ovulation, Cyp19A1 that codes for aromatase, essential for biosynthesis of estradiol- 17ß (E2), also get down- regulated but appears to get up- regulated at later time points in the estrous cycle to have critical role in E2 secretion. In primates and rodents, higher expression and higher E2 levels has been observed in CL. Surprisingly, in the recently carried out gene expression profiling of PGF2a- induced luteolysis studies in the bovine species [GSE27961], it was observed that expression of one of the earliest genes that was down- regulated was Cyp19A1 in the CL. However, the specific role of E2 in the regulation of CL function remains poorly defined. Thus, in the present study, efforts were made to examine the temporal changes in the global gene expression profile in the CL of pregnant rats after treatment with aromatase inhibitor (AI), Anastrozole, and E2 supplementation. The results obtained will further expand our knowledge on E2 target/responsive genes and the basic mechanism(s) that regulates the CL function. Key words: CL, E2, AI, Gene expression
Expression data from the mammary gland of ovariectomized (ovx) rats treated for three days with E2, 3-MC, E2+3-MC
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE64636
Tags: unclassified
Summary: The study was designed to see the overall gene-expression change in the mammary gland induced by AHR ligand 3-MC alone and in combination with E2.
Symbol: Expression data from the mammary gland of ovariectomized (ovx) rats treated for three days with E2, 3...-MC, E2+3-MC
Expression data from the uterus of ovariectomized young adult rats treated for three days with E2, 3-MC, E2+3-MC
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE95783
Tags: unclassified
Summary: The study was designed to see the overall gene-expression change in the uterus induced by E2, the AHR ligand 3-MC alone and in combination with E2.
Symbol: Expression data from the uterus of ovariectomized young adult rats treated for three days with E2, 3-...MC, E2+3-MC
Expression data from yeast strain containing CDC34tm allele compared to WT
(Saccharomyces cerevisiae)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by SGD
ID: GEO:GSE8453
Tags: protein modification
Summary: Cdc34 is an essential E2 ubiquitin conjugating enzyme found in nearly all eukaryotes
Transcriptomic analysis of the estrogenic effect of soy protein isolate in rat uterus
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE69819
Tags: unclassified
Summary: There are concerns regarding possible reproductive toxicity from consumption of soy including an increased risk of endometriosis and endometrial cancer. We used global uterine gene expression profiles in adult ovariectomized (OVX) female rats assessed by RNAseq to examine the estrogenicity of soy protein isolate (SPI) and the potential for feeding SPI to alter estrogen signaling in the uterus. Rats were fed AIN93G diets made with casein (CAS) or SPI from postnatal day (PND) 30. Rats were OVX on PND 50 and infused with 17 beta-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05) and significantly altered expression of 2084 uterine genes. In contrast, SPI feeding had no effect on uterine weight and only altered expression of 177 genes. Overlap between E2 and SPI genes was limited to 69 genes (3%). GO analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of ER alpha to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were cancer pathways and extracellular organization. SPI feeding up-regulated uterine PPAR signaling and fatty acid metabolism. The combination of E2 and SPI feeding resulted in significant regulation of 715 fewer genes relative to E2 alone. In a separate experiment, the combination of E2 and SPI reversed the ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA). These data suggest SPI does not act as a weak estrogen in the uterus but appears to be a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and to be anti-estrogenic in the presence of endogenous estrogens.
Different effects of 17 beta estrodial and soy protein isolate on bone gene expression in the pre-pubertal female rats
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE30862
Tags: unclassified
Summary: Beneficial effects of a soy diet on bone quality have been assumed to be due to the putative estrogenic actions of isoflavones. We studied the effects of soy protein isolate (SPI) on bone quality and compared these effects to 17ß-estradiol (E2) in pre-pubertal rats. Female rats were weaned to a control diet with or without E2 (0.1, 1, 10 µg/kg/d), or SPI-containing diet with or without E2 (10 µg/kg/d) for 14 days beginning on postnatal day 20. In long bones from SPI-fed rats, only cancellous bone mineral density (BMD) was increased (p<0.05), while cortical BMD was decreased accompanied by lower bone strength compared to control casein-fed rats (p<0.05). In sharp contrast, 10 µg/kg/d E2 not only increased trabecular BMD, but also cortical BMD compared to controls. Rats treated with the combination of SPI and E2 had an intermediate bone effect. SPI increased while E2 decreased bone turnover, and increased trabecular BMD by both E2 and SPI was associated with decreased serum sclerostin levels. Microarray analysis revealed 652 genes regulated by SPI diet, 491 genes regulated by E2, and 266 genes regulated in common by both SPI diet and E2 compared to rats fed casein. The expression of caveolin-1, a protein localized in cell membrane, was down-regulated (p<0.05) in rats fed SPI, but not by E2 compared to rats fed casein. Down-regulated caveolin-1 by SPI was associated with increased BMP2, Smad and Runx2 expression in bone and osteoblasts (p<0.05). These results suggest SPI consumption results in significant non-classical estrogenic stimulation of cancellous bone formation prior to puberty, but may have adverse effects on overall bone quality and strength at this developmental stage as a result of reduced cortical bone formation.
High-Throughput (HTP) Dataset Index metadata provided by SGD
ID: GEO:GSE253055
Tags: cell aging, evolution
Summary: Yeast has proven to be a useful model system for aging studies, including CR effects. We report here that yeast adapted through in vitro evolution to the severe cellular stress caused by loss of the Ulp2 SUMO-specific protease exhibit both enhanced growth rates and replicative lifespan, and they have altered gene expression profiles similar to those observed in CR. Notably, in certain evolved ulp2Δ lines, a dramatic increase in the auto-sumoylation of Ubc9 E2 SUMO-conjugating enzyme results in altered regulation of multiple targets involved in energy metabolism and translation at both transcriptional and post-translational levels. This increase is essential for the survival of aged cells and CR-mediated lifespan extension
Symbol: Auto-sumoylation of the Ubc9 E2 SUMO-conjugating Enzyme Extends Cellular Lifespan
Name: Auto-sumoylation of the Ubc9 E2 SUMO-conjugating Enzyme Extends Cellular Lifespan
miRNA Expression data from the uterus of ovariectomized young adult rats treated for three days with E2
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE95790
Tags: unclassified
Summary: The study was designed to see the overall ncRNA-expression change in the uterus induced by E2
Symbol: miRNA Expression data from the uterus of ovariectomized young adult rats treated for three days with E2
Name: miRNA Expression data from the uterus of ovariectomized young adult rats treated for three days with E2
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-25615, GEO:GSE25615
Tags: WT vs. mutant, genotype
Summary: Transcriptional profilling of 60 day old prostate tissue from Rb1F/F:Trp53F/F:PB-Cre4 or Rb1R654W/F:Trp53F/F:PB-cre4 mice versus wild type prostate tissue. Profiles used to compare deregulation of known E2F target genes in prostate tissue expressing a mutant Rb1 gene to tissue lacking Rb1 expression. Tissue from two Rb1F/F:Trp53F/F:PB-Cre4 (null) mice or two Rb1654/F:Trp53F/F:PB-cre4 (mutant) mice compared to a pool of tissue from 3 wild type mice using two color arrays.
Symbol: Rb1 E2F binding deficient mutant
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-67989, GEO:GSE67989
Tags: WT vs. mutant, genotype
Summary: The effect of E2F1 loss on gene expression in testicular tissue was analyzed in 20-day old E2F1-/-, E2F1+/- mice. The hypothesis was that there would be clear changes in expression of genes related to cell cycle machinery. The results show that E2F1 has wider implications in gene expression dynamics in testicular cell types than merely controlling cell cycle related genes. Total RNA obtained from testis tissue of 20-day-old E2F1-/- (KO), E2F1+/- (HZ) and E2F1+/+ mice (WT).
Symbol: Genome-wide analysis of E2F1 dependent gene expression in mouse testicular tissue
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by SGD
ID: GEO:GSE254981
Tags: cell aging, evolution
Summary: Yeast has proven to be a useful model system for aging studies, including CR effects. We report here that yeast adapted through in vitro evolution to the severe cellular stress caused by loss of the Ulp2 SUMO-specific protease exhibit both enhanced growth rates and replicative lifespan, and they have altered gene expression profiles similar to those observed in CR. Notably, in certain evolved ulp2Δ lines, a dramatic increase in the auto-sumoylation of Ubc9 E2 SUMO-conjugating enzyme results in altered regulation of multiple targets involved in energy metabolism and translation at both transcriptional and post-translational levels. This increase is essential for the survival of aged cells and CR-mediated lifespan extension
Symbol: Auto-sumoylation of the Ubc9 E2 SUMO-conjugating Enzyme Extends Cellular Lifespan (RNA-Seq)
Name: Auto-sumoylation of the Ubc9 E2 SUMO-conjugating Enzyme Extends Cellular Lifespan (RNA-Seq)
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE149025
Tags: WT vs. mutant, genotype
Summary: In the mouse, long-term silencing by CpG island DNA methylation is specifically targeted to germline genes in somatic cells, however the molecular mechanisms of this specificity remain unclear. Here we demonstrate that the transcription factor E2F6, a member of the polycomb repressive complex 1.6 (PRC1.6), is critical to target and initiate epigenetic silencing at germline genes in early embryogenesis. Genome-wide, E2F6 binds preferentially to CpG islands in embryonic cells. E2F6 cooperates with MGA to silence a subgroup of germline genes in mouse embryonic stem cells and in vivo, a function that critically depends on the E2F6 marked box domain. Furthermore, inactivation of E2f6 leads to a failure to deposit CpG island DNA methylation at these genes during implantation. Finally, we show that E2F6 is required to initiate epigenetic silencing in early embryonic cells but becomes dispensable for the maintenance in differentiated cells. Our findings elucidate the mechanisms of epigenetic targeting of germline genes and provide a paradigm for how transient repression signals by DNA-binding factors in early embryonic cells are translated into long term epigenetic silencing during mammalian development. We mapped E2F6 binding sites in mouse ES cells by ChIP-seq. We studied the role of E2F6 in gene expression by performing RNA-seq in triplicates in WT and E2f6-/- mouse ES cells and E8.5 embryos. To study the role of E2F6 in DNA methylation, we performed Whole Genome Bisulfite Sequencing (WGBS) in a WT and E2f6-/- embryo, as well as Reduced Representation Bisulfite Sequencing (RRBS) in WT and E2F6-/- ES cells, E8.5 embryos (two replicates), adult tissues (brain, muscle, kidney, three replicates), primary MEFs (two replicates) and MEF Crispr-Cas9 clones (two replicates).
Symbol: Role of E2F6 in gene expression and DNA methylation during mouse development
An E2F1-Dependent Gene Expression Program That Determines the Balance Between Proliferation and Cell Death
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE9496
Tags: unclassified
Summary: Keywords: PI3K dependent modulation of E2F1 gene expression measured by Affymetrix gene expression analysis
Symbol: An E2F1-Dependent Gene Expression Program That Determines the Balance Between Proliferation and Cell
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-11066, GEO:GSE11066
Tags: pregnancy, WT vs. mutant, genotype
Summary: We have compared an involution timecourse for wild type and E2F3 heterozygous mice on the Operon 3.0 platform. Three mice were taken for each genotype at each timepoint (Involution day 0, 1, 2, 3 and 4) and RNA was prepared from the mammary glands. The RNA from each mouse was pooled and run as an individual sample. Keywords: Mouse Mammary Gland RNA 5 timepoints, 2 genotypes, 3 replicates per timepoint.
Symbol: Expression data from an involution time course in wild type and E2F3 +/- mice
The E2 SUMO-conjugating enzyme UBE2I is essential for chromatin dynamics and transcriptional silencing in mouse oocytes
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE218484
Tags: WT vs. mutant, genotype
Summary: In mammals, meiotically competent oocytes develop cyclically during ovarian folliculogenesis. During their development, prophase I arrested oocytes are highly transcriptionally active in preparation for the resumption of meiosis and early stages of embryogenesis prior to the maternal to zygotic transition. Defective oocyte development during folliculogenesis leads to meiotic defects, aneuploidy, follicular atresia, or non-viable embryos. SUMOylation, a dynamic post-translational protein modification, is essential for oocyte development during folliculogenesis and to regulate meiotic maturation in mice. We generated a novel oocyte-specific knockout of Ube2i, the sole SUMO E2 ligase, to test its role growing ovarian follicles using Zp3-cre. Ube2i Zp3-cre+ female mice are sterile with oocytes with defects in meiotic progression but not meiotic resumption. Importantly, fully grown oocytes do not silence transcription and prematurely activate the zygotic transcriptional program. This work uncovers unknown functions of UBE2i as a key orchestrator of chromatin and transcriptional regulation in oocytes. We performed RNA-sequencing analysis on 17 individual control and 17 individual Ube2i cKO oocytes
Symbol: The E2 SUMO-conjugating enzyme UBE2I is essential for chromatin dynamics and transcriptional silencing
Name: The E2 SUMO-conjugating enzyme UBE2I is essential for chromatin dynamics and transcriptional silencing
Transcription profiling of pancreas from wild type and E2F1 knock-out mice to investigate insulin secretion control
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-MEXP-2243
Tags: WT vs. mutant, genotype
Summary: Total RNA was extracted from E2F1 +/+ and -/- pancreas and analysed by global gene expression
Symbol: Transcription profiling of pancreas from wild type and E2F1 knock-out mice to investigate insulin secretion
In vivo imaging and deep learning tools expose two distinct E2F cell cycle transcriptional relays (in preparation)
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE118851
Tags: baseline, cell type, developmental stage
Summary: Purpose: We used next-generation sequencing (NGS) to identify genes which oscillate during cell cycle in embryos in mRNA level Methods: Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) bi-transgenic mice (mKO2-hCDT1;mAG-hGEM) mRNA profiles of Embryo day 10.5, 11.5 and 13.5 were generated for deep sequencing. The reads were aligned using STAR program and . RT-PCR validation was performed using SYBR Green assays Results: Genes consistently expressed >2 log fold higher (with an adjusted P-value < 0.05) in DR, YE, or GR samples than in BR samples, were denoted 'proliferation-related.' Of these 258 proliferation-related genes, 86 were previously reported as periodically expressed during the cell cycle. The majority of genes whose expression was enriched in BR samples (267 genes) were related to cell differentiation and non-proliferative processes, and were thus classified as 'quiescent-related.' In agreement with measurements made in cell culture systems, E2f1-3a and E2f7-8 mRNA levels increased in cycling cells when compared to cells in G0, with maximum levels observed in S and G2, albeit the increased expression of E2f7-8 was more pronounced. The mRNA levels of E2f3b, E2f4, E2f5 and E2f6 remained relatively unchanged among the various cell cycle fractions Conclusions: Our research use NGS to deeply study the cell-cyle related gene expression in vivo. The data analysis work flows reported here provides gene expression information regarding to different cell cycle phase and embryo age. Examine the gene expression for different cell cycle phases (BR,DR,YE,GE) using FUCCI wild type 10.5, 11.5 and 13.5 embryos (E10.5,E11.5 and E13.5)
Symbol: In vivo imaging and deep learning tools expose two distinct E2F cell cycle transcriptional relays (in
Aqp1 overexpression may enhance glioma tumorigenesis by interacting with the transcriptional regulation networks of Foxo4, Maz, and E2F families
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE137733
Tags: unclassified
Summary: Gliomas is the most common and aggressive primary brain tumor. The C6 glioma cell line has been widely used for decades as experimental model system for the study of glioblastoma growth and invasion. Recently, aquaporin-1 (Aqp1) is reported to facilitate cell migration and potentially involved in tumor progression. Here we overexpressed Aqp1 in C6 cells to examine its potential role in glioblastoma. We found overexpression of Aqp1 in C6 cells significantly increased cell viability and cell migration. The upregulated genes were enriched for cell mobility and glioblastoma. Transcriptional factor binding analysis indicates the upregulated genes were regulated by FOXO4, MAZ, and E2F TF families, which are known factors involved in cell cycle control and cancer progression. Our study suggests Aqp1 is potentially involved in gliomas formation by interacting with the transcriptional regulation networks of FOXO4, MAZ, and E2F TF families.
Symbol: glioma tumorigenesis by interacting with the transcriptional regulation networks of Foxo4, Maz, and E2F
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-57324, GEO:GSE57324
Tags: WT vs. mutant, genotype
Summary: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the production of antibodies to self-nucleic acids, immune complex deposition and tissue inflammation such as glomerulonephritis. Innate recognition of molecular complexes containing self-DNA and RNA and the ensuing production of type I interferons (IFN) contribute to SLE development. Plasmacytoid dendritic cells (pDCs) have been proposed as a relevant source of pathogenic IFN in SLE; however, their net contribution to the disease remains unclear. We addressed this question using haplodeficiency of the pDC-specific transcription factor E2-2 (Tcf4), which causes a specific impairment of pDC function in otherwise normal animals. We report that Tcf4+/- animals were significantly protected from SLE-like disease caused by the overexpression of the endosomal RNA sensor Tlr7. The protection was also observed after the monoallelic deletion of Tcf4 specifically in the dendritic cell lineage. Furthermore, Tcf4 haplodeficiency in the B6.Sle1.Sle3 multigenic model of SLE ameliorated key disease manifestations including anti-DNA antibody production, immune activation and glomerulonephritis. These results provide genetic evidence that pDCs are critically involved in SLE pathogenesis, confirming their potential utility as therapeutic targets in the disease. Cellular suspension were obtained from the spleen of wild type, Sle1.3 and Sle1.3/E2-2het mice. 10 million of cells were used to isolate RNA from each sample. After RNA isolation a microarray analysis using the Ambion WT labeling kit was done. Expression was analyzed using Affymetrix Mouse Gene 1.0 ST. 2 Wild type mice, 3 Sle1.3 and 3 Sle1.3/E2-2 het mice were used for the analysis.
Symbol: expression analysis in the spleen of wild type, Sle1.3 (lupus mice) and Sle1.3 mice haplodeficient for E2
Association of Cellular and Molecular Responses in the Rat Mammary Gland to 17beta-Estradiol with Susceptibility to Mammary Cancer
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE49548
Tags: unclassified
Summary: We are using ACI and BN rats, which differ markedly in their susceptibility to 17beta-Estradiol (E2)-induced mammary cancer, to identify genetic variants and environmental factors that determine mammary cancer susceptibility. The objective of this study was to characterize the cellular and molecular responses to E2 in the mammary glands of ACI and BN rats to identify qualitative and quantitative phenotypes that associate with and/or may confer differences in susceptibility to mammary cancer. Female ACI and BN rats were treated with E2 for 1, 3 or 12 weeks and cell proliferation, apoptosis, differentiation and gene expression were evaluated. The luminal epithelium of ACI rats exhibited a rapid and sustained proliferative response to E2. By contrast, the proliferative response exhibited by the mammary epithelium of BN rats was restrained and transitory. Moreover, the epithelium of BN rats appeared to undergo differentiation in response to E2, as evidenced by production of milk proteins as well as luminal ectasia and associated changes in the extracellular matrix (ECM). Marked differences in expression of genes that encode proteins with well-defined roles in mammary gland development (Pgr, Wnt4, Tnfsf11, Prlr, Stat5a, Areg, Gata3), differentiation and milk production (Lcn2, Spp1), regulation of extracellular environment (Mmp7, Mmp9), and cell-cell or cell-ECM interactions (Cd44, Cd24, Cd52) were observed. We propose that these cellular and molecular phenotypes are heritable and may underlie, at least in part, the differences in mammary cancer susceptibility exhibited by ACI and BN rats.
Estrogen regulated genes in rat testes and their relationship to recovery of spermatogenesis after irradiation
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE24672
Tags: unclassified
Summary: Despite numerous observations of effects of estrogens on spermatogenesis, identification of estrogen-regulated genes in the testis is limited. We previously showed in rats, in which irradiation had completely blocked spermatogonial differentiation, that testosterone (T) suppression with GnRH-antagonist and antiandrogen stimulated spermatogenic recovery and addition of estradiol (E2) to this regimen accelerated this recovery. We report here the global changes in testicular cell gene expression induced by the E2 treatment. By minimizing the changes in other hormones and also having concurrent data on the regulation of the genes by those hormones, we were able to dissect the effects of estrogen on gene expression, independent of gonadotropin or T changes. Expression of 20 genes, largely in somatic cells, was up- or down-regulated between 2- and 5-fold by E2. There were also early germ cell genes whose expression increased but this was a result of a small increase in spermatogonial numbers. The striking enrichment of transcripts not corresponding to known genes among the E2-downregulated probes led to the identification of one as micro-RNA miR-34a. We propose that genes whose expression levels are altered in one direction by irradiation and in the opposite direction by both T suppression and E2 treatment are candidates for controlling the block in differentiation. Several genes, including insulin-like 3 (Insl3), satisfied those criteria. If they are indeed involved in the inhibition of spermatogonial differentiation, they may be candidate targets for clinical treatments to enhance recovery of spermatogenesis following gonadotoxic exposures, such as those resulting from cancer therapy.
Examination of CA1 hippocampal DNA methylation as a mechanism for closing of estrogen’s critical window
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE167038
Tags: unclassified
Summary: The study presents several novel findings that relate to the idea that alterations in DNA methylation occurs during aging and may be linked to senescent physiology, including a decline in circulating E2. In addition, the evidence has been provided that DNA methylation contributes to the closing of the critical window for E2 effects on synaptic function.
Effects of Follicle Stimulating Hormone on Adipose Tissue Metabolic Health After Loss of Ovarian Function
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE247952
Tags: unclassified
Summary: Loss of ovarian function imparts increased susceptibility to obesity and metabolic disease. These effects are largely attributed to decreased estradiol (E2), but the role of increased follicle stimulating hormone (FSH) in modulating energy balance has not been fully investigated. Previous work that inhibited FSH activity in mice suggested this hormone may play a part in modulating body weight and energy expenditure after ovariectomy. We used an alternate approach to experimentally isolate the individual and combined contributions of FSH and E2 in mediating energy imbalance and changes in tissue-level metabolic health. Female Wistar rats were ovariectomized and given the GnRH antagonist degarelix to suppress FSH production. E2 and FSH were then added back individually and in combination for a period of 3 weeks. Energy balance, body mass composition, and transcriptomic profiles of individual tissues were obtained. In contrast to previous studies, ablation and replacement of FSH in our paradigm had no effect on body weight, body composition, food intake, or energy expenditure. We did, however, observe organ-specific effects of FSH that produced unique transcriptomic signatures of FSH in retroperitoneal white adipose tissue. These included reductions in biological processes related to lipogenesis and carbohydrate transport. Additionally, rats administered FSH had reduced liver triglyceride concentration (p<0.001), which correlated with FSH-induced changes at the transcriptomic level. While not appearing to modulate energy balance after loss of ovarian function in rats, FSH may still impart tissue-specific effects in the liver and white adipose tissue that might affect the metabolic health of those organs.
High-Throughput (HTP) Dataset Index metadata provided by SGD
ID: GEO:GSE22271
Tags: chemical stimulus
Summary: The target of rapamycin (TOR) plays a central role in eukaryotic cell growth control
Symbol: Saccharomyces cerevisiae temperature-sensitive strains specific for SCF core components (Skp1, Cullin (Cdc53), E2
Name: Saccharomyces cerevisiae temperature-sensitive strains specific for SCF core components (Skp1, Cullin (Cdc53), E2
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-14512, GEO:GSE14512
Tags: WT vs. mutant, genotype
Summary: Muscle ring finger (MuRF) proteins have been implicated in the transmission of mechanical forces to nuclear cell signaling pathways through their association with the sarcomere. We recently reported that MuRF1, but not MuRF2, regulated pathologic cardiac hypertrophy in vivo. This was surprising since MuRF1 and MuRF2 interact redundantly with sarcomeric proteins in yeast two hybrid studies, and form both homo- and hetero-dimers with each other. To determine if MuRF1 and MuRF2 were functionally redundant during development, we created mice lacking either 3 or 4 of the MuRF1 and MuRF2 alleles and compared them functionally. Surprisingly, only mice missing all four MuRF1 and MuRF2 alleles (MuRF1-/-//MuRF2-/-) developed a spontaneous hypertrophic cardiomyopathy - mice that were null for one of the genes, but heterozygous for the other (i.e. MuRF1-/-//MuRF2+/- or MuRF1+/-//MuRF2-/-) were phenotypically identical to wild type mice. Electron microscopy of the hearts of MuRF1-/-//MuRF2-/-(MuRF1/MuRF2 DN) mice identified altered Z disc and M line architecture, and a distinct swelling of mitochondria. MuRF1-/-//MuRF2-/- mouse hearts displayed increased expression of genes associated with fetal cardiac metabolism, including smooth muscle actin and b myosin heavy chain, suggesting that the cardiac hypertrophy seen in these mice was associated with a reversion to a fetal gene program. Despite our prediction that we would also see an increase in glucose compared to fatty acid oxidation (another trait of fetal cardiac metabolism) we saw that MuRF1-/-//MuRF2-/- heart homogenates oxidized significantly less glucose compared to controls, suggesting an important role for MuRF1 and MuRF2 in the regulation of glucose metabolism in vivo. This study identifies a previously unreported redundancy in the function of MuRF proteins in normal cardiac development. Keywords: Genetic modification. Four strain-matched groups of 12 week old mice were investigated: 1) MuRF1 -/- MuRF2 -/-; 2) MuRF1 +/+ MuRF2 +/+; 3) MuRF1 -/- MuRF2 +/-; 4) MuRF1 +/- MuRF2 -/-. Biological replicates: 4 WT, 4 MuRF1 -/- // MuRF2 -/-, 4 MuRF1 +/- //MuRF2 -/-, 4 MuRF1 -/- // MuRF2 +/-. Hearts harvested. One replicate per array.
Symbol: and MuRF2 are Necessary but Functionally Redundant During Developmental Cardiac Growth and Regulate E2F1
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by SGD
ID: GEO:GSE131639
Tags: chromatin organization, disease
Summary: The conserved yeast E3 ligase Bre1 and its partner E2 Rad6 monoubiquitinate histone H2B across gene bodies during the transcription cycle. While processive ubiquitination might in principle arise from Bre1/Rad6 traveling with RNA polymerase II, we provide a different explanation. Here we implicate liquid-liquid phase separation as the underlying mechanism. Biochemical reconstitution shows that Bre1 binds the scaffold protein Lge1, whose intrinsically disordered region phase separates via dynamic, multivalent interactions. The resulting condensates comprise a core of Lge1 encapsulated by an outer catalytic shell of Bre1. This layered liquid recruits Rad6 and the nucleosomal substrate, accelerating H2B ubiquitination. In vivo, the condensate-forming region of Lge1 is required to ubiquitinate H2B in gene bodies beyond the +1 nucleosome. Our data suggest that layered condensates of histone modifying enzymes generate chromatin-associated reaction chambers with augmented catalytic activity along gene bodies. Equivalent processes may occur in human cells, causing neurological disease when impaired.
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-13753, GEO:GSE13753
Tags: WT vs. mutant, developmental stage, genotype
Summary: Homozygous mutation of the murine retinoblastoma tumor suppressor gene, Rb, results in embryonic lethality between E13.5 and E15.5 with defects in cellular proliferation, differentiation and apoptosis. Many of these defects are suppressed by mutation of an activating E2F, E2f1 or E2f3, indicating that they are key downstream targets of the retinoblastoma protein, pRB. In this study, we assess how E2F4 contributes to the developmental consequences of pRb-loss. In stark contrast to the activating E2Fs, the homozygous mutation of E2f4 shortened the lifespan of Rb-/- embryos. This resulted from an exacerbation of the placental defect of the Rb-/- mice indicating that E2F4 and pRB cooperate in the development of this tissue. Further analyses indicated that this defect reflects an increase in trophectoderm-like cells. Under conditions where the placenta was wild-type but the embryo mutant for E2f4 and pRb embryos survived to birth and exhibited all of the defects that were observed in the E2f4 and Rb single mutant embryos. Thus, while pRB and E2F4 cooperate in placental development, they play largely non-overlapping roles the development of many embryonic tissues. Experiment Overall Design: In one experiment, embryonic Day 13.5 placentas from wild-type and Rb -/- knock-out mice were compared. In the second experiment, embryonic day 11.5 placentas from wild-type and Rb -/-;E2f4 -/- double knock-out mice were compared.
Symbol: mice and embryonic day 11.5 placentas from wild-type and Rb -/-;E2f4 -/- double knock-outs reveals E2F4
Gene modulation in acetic acid-induced oral ulcerative mucositis
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE83349
Tags: unclassified
Summary: To reveal the molecular mechanisms underlying oral ulcerative mucositis-induced pain, we investigated putative pain-associated mediators, pain-related behaviors and gene modulation in a rat oral mucositis model. On day 1 after acetic acid treatment, the mucosal area showed slight redness and swelling but no evidence of ulceration or pain induction. On day 2, oral ulcers were obvious, as was the induction of spontaneous and mechanical pain. In the treated mucosal area, bacterial loading and prostaglandin E2 increased beginning on day 2; no significant changes were observed on day 1. DNA microarray analysis of trigeminal ganglion tissue collected on day 2 identified 32 significantly regulated genes (>1.5-fold change in expression). The up-regulation of the top 3 genes, Hamp (hepcidin antimicrobial peptide), Reg3b (regenerating islet-derived 3ß) and Serpina3n (serine peptidase inhibitor A3N), was validated through quantitative RT-PCR. Systemic antibiotic pre-treatment did not increase the mRNA levels. Therefore, we conclude that the oral ulcerative mucositis-induced pain is caused by infectious inflammation of the ulcerative area and stimulates anti-bacterial and anti-peptidase gene expressions in sensory neurons.
Expression data from the hearts of aged Norway Brown rats (18-22 months-old)
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE30851
Tags: unclassified
Summary: Despite an abundance of evidence to the contrary from animal studies, large clinical trials on humans have shown that estrogen administered to post-menopausal women increases the risk of cardiovascular disease. However, timing may be everything, as estrogen is often administered immediately after ovariectomy (ovx) in animal studies, while estrogen administration in human studies occurred many years post-menopause. This study investigates the discrepancy by administering 17ß-estradiol (E2) in a slow-release capsule to Norway Brown rats both immediately following ovx and 9 weeks post-ovx (Late), and studying differences in gene expression between these 2 groups as compared to age-matched ovx and sham operated animals. Two different types of microarray were used to analyze the left ventricles from these groups: an Affymetrix array (2 samples/group, each sample contained total RNAs pooled from 3 rats) and an Inflammatory Cytokines and Receptors PCR array (N=4 /group). Key genes were analyzed by western blotting. Ovx without replacement led to an increase in caspase 3, caspase 9, calpain 2, MMP9, and TNFa. Caspase 6, STAT3, and CD11b increased in the Late group, while TIMP2, MMP14, and collagen I a1 were decreased. MADD and fibronectin were increased in both Ovx and Late. TNFa protein levels increased with Late replacement. Many of these changes were prevented by early E2 replacement. These findings suggest that increased TNFa may be involved in some of the deleterious effects of delayed E2 administration seen in human studies.
High-Throughput (HTP) Dataset Index metadata provided by SGD
ID: GEO:GSE146296
Tags: transcriptional regulation
Summary: Project abstract : The trimethylation of histone H3 lysine 4 (H3K4me3) is a crucial factor in defining the promoter regions of active genes in all eukaryotes ranging from Saccharomyces cerevisiae (yeast) to humans. In budding yeast, this trimethylation process facilitated by the Set1 complex results in H3K4me3 requiring a prior mono-ubiquitination at the histone H2BK123 residue (H2Bub) by E2 enzyme Rad6 and E3 enzyme Bre1. A previous in vitro study suggested that ubiquitinated H2B directly facilitates H3K4me3. However, even low levels of global H2Bub is sufficient for the required H3K4me3 in yeast cells, thereby indicating that other factors resulting in the H2Bub-dependent H3K4me3 remain unknown. This study revealed the high level of correlation of H3K4me3 with chromatin recruitment of Rad6 at the genome-wide level. Rad6 is confirmd to interact and co-localize with Swd2/Cps35, a key factor for the H2Bub-dependent H3K4me3 in genes with high levels of H3K4me3 and intronic genes rather than non-intronic genes. This study therefore provides a mechanistic insight of the H2Bub-Rad6- Swd2/Cps35-H3K4me3 axis and its potential role in RNA biogenesis.
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by SGD
ID: GEO:GSE139633
Tags: chromatin organization
Summary: Rad6 E2 ubiquitin-conjugating enzyme and Bre1 E3 ubiquitin ligase catalyze histone H2B Lysine-123 monoubiquitination (H2Bub1), which stabilizes nucleosomes and regulates the trans-histone H3K4 and K79 methylation during gene transcription and other nuclear processes. The interaction interfaces within the Rad6-Bre1-containing H2B ubiquitin-conjugating complex has remained unknown. By solving the crystal structure of Rad6 along with a non-RING domain N-terminal region of Bre1, we report a beta-turn in Rad6's so-called backside region away from catalytic pocket as a binding site for a homodimer of Bre1 E3 ligase. Using quantitative ChIP-seq or ChIP-Rx, we further demonstrate that Rad6's backside beta-turn residues also govern the chromatin binding dynamics of the Rad6-Bre1 complex.
Effect of Rad6 backside beta-turn mutations on gene expression
(Saccharomyces cerevisiae)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by SGD
ID: GEO:GSE139632
Tags: chromatin organization
Summary: Rad6 E2 ubiquitin-conjugating enzyme and Bre1 E3 ubiquitin ligase catalyze histone H2B Lysine-123 monoubiquitination (H2Bub1), which stabilizes nucleosomes and regulates the trans-histone H3K4 and K79 methylation during gene transcription and other nuclear processes. The interaction interfaces within the Rad6-Bre1-containing H2B ubiquitin-conjugating complex have remained unknown. By solving the crystal structure of Rad6 along with a non-RING domain N-terminal region of Bre1, we report a beta-turn in Rad6's so-called backside region away from catalytic pocket as a binding site for a homodimer of Bre1 E3 ligase. Using quantitative ChIP-seq or ChIP-Rx, we further demonstrate that Rad6's backside beta-turn residues also govern the chromatin binding dynamics and transcriptional regulatory functions of the Rad6-Bre1 complex.
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-70048, GEO:GSE70048
Tags: pregnancy, baseline
Summary: 2-methoxyestradiol (2ME2) induces mammary gland differentiation through amphiregulin-EGFR mediated signaling: molecular distinctions from the mammary gland of pregnant mice.High levels of 2ME2 are observed in the late stages of pregnancy. We investigated the role of 2ME2 on normal mammary gland development. Large scale gene expression assays were performed using Affymetrix GeneChips in pursuit of detailed molecular basis. (1) Mammary glands of wild type FVB mice administered 75 or 150 mg/kg of 2ME2 (2) Mammary glands of normal FVB/Nj mice (i) at day 16 of pregnancy, (ii) day 2 of lactation (iii) day 30 of post-lactation, and (3) mammary epithelial SCp2 cells after 6, 24 and 48 hours of 10 micromol 2ME2 treatment were examined. In vivo studies revealed that 2ME2 treatment up regulates the expression of amphiregulin. The clue to the role of 2ME2 in differentiation comes from studies in vitro which detected down regulation of inhibitor of differentiation (Id-1) gene and consequent up regulation of amphiregulin. The differentiation of E2 negative SCp2 cells by 2ME2 indicate estradiol independent mechanism. For details, please see our paper in Endocrinology 2006. **NOTE: Migrated from caArray 1.x, identifier='gov.nih.nci.ncicb.caarray:Experiment:1015897590892008:1' green-00030 Assay Type: Gene Expression Provider: Affymetrix Array Designs: mg_u74av2, Mouse430_2 Organism: Mus musculus (ncbitax) Tissue Sites: murine mammary gland Material Types: cell, synthetic_RNA, organism_part, total_RNA
The ubiquitin conjugase Rad6 mediates ribosome pausing during oxidative stress
(Saccharomyces cerevisiae)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by SGD
ID: GEO:GSE226082
Tags: oxidative stress
Summary: Oxidative stress causes K63-linked ubiquitination of ribosomes by the E2 ubiquitin conjugase, Rad6. How Rad6-mediated ubiquitination of ribosomes affects translation, however, is unclear. We therefore performed Ribo-seq and Disome-seq in Saccharomyces cerevisiae, and found that oxidative stress caused ribosome pausing at specific amino acid motifs, and this also led to ribosome collisions. However, these redox pausing signatures were lost in the absence of Rad6 but did not depend on the ribosome-associated quality control (RQC) pathway. We also found that Rad6 is needed to inhibit overall translation in response to oxidative stress and its deletion leads to increased expression of antioxidant genes. Finally, we observed that the lack of Rad6 leads to changes during translation initiation that affect activation of the integrated stress response (ISR) pathway. Our results provide a high-resolution picture of the gene expression changes during oxidative stress and unravel an additional stress response pathway affecting translation elongation.