Version: 8.0.0Date: Tue Jan 28 2025
HTP Dataset Index
Brdt KO mice: Wild-type vs. Mutant
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE72786
Tags: WT vs. mutant, genotype
Summary: Transcriptional profiling of mouse pituitary tissue comparing WT with Brdt KO mice. Goal was to determine the effects of Brdt absence on pituitary gene expression. Four pools each of total RNA (three mice per pool) extracted from Brdt-/- and wild-type mice. Biological replicates: 2 WT replicates, 2 Brdt KO replicates.
Symbol: Brdt KO mice: Wild-type vs. Mutant
Name: Brdt KO mice: Wild-type vs. Mutant
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE136752
Tags: WT vs. mutant, genotype
Summary: Spermatogenesis is a complex process of sperm generation, including mitosis, meiosis, and spermiogenesis. During spermiogenesis, histones in post-meiotic spermatids are removed from chromatin and replaced by protamines. Although histone-to-protamine exchange is important for sperm nuclear condensation, the underlying regulatory mechanism is still poorly understood. Here, we identify PHD finger protein 7 (PHF7) as an E3 ubiquitin ligase for histone H3K14 in post-meiotic spermatids. Generation of Phf7-deficient mice and Phf7 C160A knockin mice with impaired E3 ubiquitin ligase activity reveals defects in histone-to-protamine exchange caused by dysregulation of histone removal factor Bromodomain, testis-specific (BRDT) in early condensing spermatids. Surprisingly, E3 ubiquitin ligase activity of PHF7 on histone ubiquitination leads to stabilization of BRDT by attenuating ubiquitination of BRDT. Collectively, our findings identify PHF7 as a critical factor for sperm chromatin condensation and contribute to mechanistic understanding of fundamental phenomenon of histone-to-protamine exchange and potential for drug development for the male reproduction system. single cell RNA sequencing performed with testicular cells from Phf7 f/f and Phf7 tKO mice.
Symbol: PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis
Name: PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-33132, GEO:GSE33132
Tags: WT vs. mutant, genotype
Summary: Brdt is a testis specific member of a family of chromatin interacting proteins. All of the family members have been shown to regulate transcription. Brdt is highly expressed in round spermatids, and may play a role in transcriptional regulation in these cells. We investigated transcriptional changes in mutant round spermatids that were homozygous for a mutation in which the first bromodomain of Brdt was removed. Round spermatids were purified from seven adult animals of each genotype for each Affymetrix microarray. Purity of round spermatids was assessed by propidium iodide staining.
Symbol: Expression data from purified control and Brdt-delta-BD1 round spermatids
Bromodomain-dependent stage-specific male genome programming by Brdt [Illumina BeadArray]
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-GEOD-39909, GEO:GSE39909
Tags: WT vs. mutant, genotype
Summary: Male germ cell differentiation is a highly regulated multistep process initiated by the commitment of progenitor cells into meiosis and characterized by major chromatin reorganizations in haploid spermatids. We report here that a single member of the double bromodomain BET factors, Brdt, is a master regulator of both meiotic divisions and post-meiotic genome repackaging. Upon its activation at the onset of meiosis, Brdt drives and determines the developmental timing of a testis-specific gene expression program. In meiotic cells, Brdt initiates a genuine histone acetylation-guided programming of the genome by activating essential meiotic genes and repressing a "progenitor cells" gene expression program, while "priming" a post-meiotic gene group for further activation. At post-meiotic stages, a global chromatin hyperacetylation gives the signal for Brdt's first bromodomain to direct the genome-wide replacement of histones by transition proteins. Brdt is therefore a unique and essential regulator of male germ cell differentiation, which, by using various domains in a developmentally controlled manner, first drives a specific spermatogenic gene expression program, and later controls the tight packaging of the male genome. Total RNA obtained from testes from prepuberal mice at 17dpp and at 20dpp were compared between Brdt-/- and Brdt+/- (17dpp), between Brdt-/- and Brdt +/+ (20dpp) and between BrdtBD1del and Brdt wt mice (20dpp). In each experiments, 6 replicates of each genotype and condition were used.
Symbol: Bromodomain-dependent stage-specific male genome programming by Brdt [Illumina BeadArray]
Name: Bromodomain-dependent stage-specific male genome programming by Brdt [Illumina BeadArray]
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE212116
Tags: baseline, cell type
Summary: During meiotic prophase I, germ cells must balance transcriptional activation with meiotic recombination and chromosome synapsis, biological processes requiring extensive changes to chromatin state and structure. Here we explored the interplay between chromatin accessibility and transcription across a detailed time-course of murine male meiosis by measuring genome-wide patterns of chromatin accessibility, transcription, and processed mRNA. To understand the relationship between these parameters of gene regulation and recombination, we integrated these data with maps of double-strand break formation. Maps of nascent transcription showed that Pol II is loaded on chromatin and maintained in a paused state early during meiosis. In pachynema, paused Pol II is released in a coordinated transcriptional burst resulting in ~3-fold increase in transcription. Release from pause is mediated by the transcription factor A-MYB and the testis-specific bromodomain protein, BRDT. The burst of transcriptional activity is both temporally and spatially segregated from key steps of meiotic recombination: double strand breaks show evidence of chromatin accessibility earlier during prophase I and at distinct loci from those undergoing transcriptional activation, despite shared chromatin marks. Our findings uncover the mechanisms of transcriptional activation and how cells compartmentalize transcription and recombination during meiosis.
Symbol: Meiotic gene transcription programs are mediated by A-MYB and BRDT-dependent RNA Pol II pause release