Version: 8.0.0Date: Tue Jan 28 2025
Category
Disease
Source: DOID:10603
Definition: Not Available
Genes: Hnf1a (Mmu)...hnf1a (Dre)...hnf1a.S (Xla)...Hnf1a (Rno)...HNF1A (Hsa)
Tg(Ins2-Hnf1a)#Cbw
(Mus musculus)Allele/Variant
Source: MGI:4942165
Genes: Not Available
Synonyms: Not Available
Variant Type: unreported
Molecular Consequence: Not Available
Diseases: maturity-onset diabetes of the young type 3
Variant Name: Not Available
Symbol: Tg(Ins2-Hnf1a)#Cbw
Construct Expressed Component: Hnf1a
Gene Ontology
Source: GO:0030111
Synonyms:
- regulation of Wnt receptor signaling pathway
- regulation of Wnt receptor signalling pathway
Branch: biological process
Genes: Hnf1a (Mmu)...Hnf1a (Rno)...HNF1A (Hsa)
Source: GO:0010918
Synonyms:
- elevation of mitochondrial membrane potential
Branch: biological process
Genes: Hnf1a (Mmu)...Hnf1a (Rno)
Gene Ontology
Source: GO:0071233
Synonyms:
- cellular response to leucine
Branch: biological process
Genes: Hnf1a (Mmu)...Hnf1a (Rno)
Gene Ontology
Source: GO:0045453
Synonyms: Not Available
Branch: biological process
Genes: Hnf1a (Mmu)...Hnf1a (Rno)...HNF1A (Hsa)
Gene Ontology
Source: GO:0046323
Synonyms:
- glucose import
- glucose uptake
Branch: biological process
Genes: Hnf1a (Mmu)...Hnf1a (Rno)...HNF1A (Hsa)
Gene Ontology
Source: GO:0015721
Synonyms:
- bile acid transport
- bile salt transport
Branch: biological process
Genes: Hnf1a (Mmu)...Hnf1a (Rno)...HNF1A (Hsa)
Source: GO:0010801
Synonyms: Not Available
Branch: biological process
Genes: Hnf1a (Mmu)...Hnf1a (Rno)
Gene Ontology
Source: GO:2001171
Synonyms:
- positive regulation of ATP anabolism
- positive regulation of ATP biosynthesis
Branch: biological process
Genes: Hnf1a (Mmu)...Hnf1a (Rno)
Hepatocyte Nuclear Factors 4a and 1a (Hnf4a and Hnf1a) Regulate Kidney Developmental Expression of Drug-Metabolizing Enzymes and Drug Transporters
(Rattus norvegicus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by RGD
ID: GEO:GSE50815
Tags: unclassified
Summary: The transcriptional regulation of drug-metabolizing enzymes and transporters (here collectively referred to as DMEs) in the developing proximal tubule is not well understood. As in the liver, DME regulation in the PT may be mediated through nuclear receptors which are thought to “sense” deviations from homeostasis by being activated by ligands, some of which are handled by DMEs, including drug transporters. Systems analysis of transcriptomic data during kidney development predicted a set of upstream transcription factors, including Hnf4a and Hnf1a, as well as Nr3c1 (Gr), Nfe2l2 (Nrf2), Ppara, and Tp53. Motif analysis of cis-regulatory further suggested that Hnf4a and Hnf1a are the main transcriptional regulators in the PT. Available expression data from tissue-specific Hnf4a KO tissues revealed that distinct subsets of DMEs were regulated by Hnf4a in a tissue-specific manner. ChIP-seq was performed to characterize the PT-specific binding sites of Hnf4a in rat kidneys at three developmental stages (prenatal, immature, adult), which further supported a major role for Hnf4a in regulating PT gene expression, including DMEs. In ex vivo kidney organ culture, an antagonist of Hnf4a (but not a similar inactive compound) led to predicted changes in DME expression, including among others Fmo1, Cyp2d2, Cyp2d4, Nqo2, as well as organic cation transporters and organic anion transporters Slc22a1(Oct1), Slc22a2 (Oct2), Slc22a6 (Oat1), Slc22a8(Oat3), and Slc47a1(Mate1). Conversely, overexpression of Hnf1a and Hnf4a in primary mouse embryonic fibroblasts (MEFs), sometimes considered a surrogate for mesenchymal stem cells, induced expression of several of these proximal tubule DMEs, as well as epithelial markers and a PT-specific brush border marker Ggt1. These cells had organic anion transporter function. Taken together, the data strongly supports a critical role for HNF4a and Hnf1a in the tissue-specific regulation of drug handling and differentiation toward a PT cellular identity.
Symbol: Hepatocyte Nuclear Factors 4a and 1a (Hnf4a and Hnf1a) Regulate Kidney Developmental Expression of Drug-Metabolizing
Gene Ontology
Source: GO:0006783
Synonyms:
- haem biosynthesis
- haem biosynthetic process
Branch: biological process
Genes: Hnf1a (Mmu)...Hnf1a (Rno)...HNF1A (Hsa)
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-MTAB-11475
Tags: WT vs. mutant, anatomical structure, genotype
Summary: Germ-line deletion of the Haster promoter region results in overexpression of Hnf1a in liver, while a variegated phenotype is observed in pancreatic islets, with overexpression or silencing of the Hnf1a gene in different cells. Mouse hybrid experiments show that both activation and silencing mechanisms occur in cis. To assess whether HASTER transcription or RNA transcripts are involved in the regulation of Hnf1a, we have generated a mouse model where the 4xSV40 polyA signal has been inserted downstream of Haster promoters (Haster-Stop allele) to terminate Haster transcription, but leaving the Haster promoter intact. Haster Stop/+ F1 mice with the Haster Stop allele from C57BL/6 origin and wild type allele from the PWK/PhJ origin were used for stain-specific RNA-seq in pancreatic islets and liver. Allele-specific quantification of Hnf1a exon 1 were used to assess the requirement of the Haster transcripts/transcription for Hnf1a expression.
Disease
Source: DOID:13619
Definition: A cholestasis resulting from causes located_in bile ducts outside the liver.
Genes: Hnf1a (Mmu)...hnf1a (Dre)...Hnf1a (Rno)...HNF1A (Hsa)...hnf1a (Xtr)
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-MTAB-11477
Tags: WT vs. mutant, genotype
Summary: Pancreas specific deletion of the Haster promoter region results in a variegated phenotype in pancreatic islets with overexpression or silencing of the Hnf1a gene. To determine the transcriptional consequence of the overexpression or silencing of Hnf1a is islet cells from the Haster pKO mice (Haster loxP/loxP;Pdx1-Cre), we performed scRNA-seq of pancreatic islets from control and adult female Haster pKO mice.
Tg(Hnf1a-RB1*)XMiu/? [background:] Not Specified
(Mus musculus)Model
Id: MGI:5312919
Synonyms: Not Available
Name: Tg(Hnf1a-RB1*)XMiu/? [background:] Not Specified
Gene Ontology
Source: GO:0001824
Synonyms: Not Available
Branch: biological process
Genes: Hnf1a (Mmu)...Hnf1a (Rno)...HNF1A (Hsa)
Gene Ontology
Source: GO:0030073
Synonyms: Not Available
Branch: biological process
Genes: Hnf1a (Mmu)...hnf1a (Dre)...Hnf1a (Rno)...HNF1A (Hsa)
Gene Ontology
Source: GO:0031016
Synonyms: Not Available
Branch: biological process
Genes: Hnf1a (Mmu)...hnf1a (Dre)...Hnf1a (Rno)...HNF1A (Hsa)
Igs2em1(CAG-HNF1A*)Plu
(Mus musculus)Allele/Variant
Source: MGI:7572409
Genes: Not Available
Synonyms: Not Available
Variant Type: unreported
Molecular Consequence: Not Available
Diseases: Not Available
Variant Name: Not Available
Symbol: Igs2HNF1A*)Plu>
Construct Expressed Component: HNF1A (Hsa)
Tg(Ins2-TCF1*P291)2Kya
(Mus musculus)Allele/Variant
Source: MGI:2386579
Genes: Not Available
Synonyms: Not Available
Variant Type: unreported
Molecular Consequence: Not Available
Diseases: maturity-onset diabetes of the young type 3
Variant Name: Not Available
Construct Expressed Component: HNF1A (Hsa)
Gene Ontology
Source: GO:0015908
Synonyms: Not Available
Branch: biological process
Genes: Hnf1a (Mmu)...Hnf1a (Rno)...HNF1A (Hsa)
Disease
Source: DOID:11714
Definition: A diabetes mellitus that manifests during pregnancy.
Genes: hnf1a (Dre)...Hnf1a (Rno)...HNF1A (Hsa)...hnf1a (Xtr)...Hnf1a (Mmu)
Gene Ontology
Source: GO:0001890
Synonyms:
- placental development
- placentation
Branch: biological process
Genes: Hnf1a (Mmu)...Hnf1a (Rno)...HNF1A (Hsa)
Gene Ontology
Source: GO:0030326
Synonyms: Not Available
Branch: biological process
Genes: Hnf1a (Rno)...HNF1A (Hsa)...Hnf1a (Mmu)
RNA-seq in control and Haster-deficient mouse livers
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:E-MTAB-11463
Tags: WT vs. mutant, genotype
Summary: The HASTER promoter region is a cis-regulatory element that stabilizes the transcription of HNF1A, preventing silencing or overexpression. We have generated a mouse model where the promoter of Haster has been specifically deleted in liver (Haster loxP/loxP; AlbCre). In liver the prevailing consequence is upregulation of HNF1A. We performed RNA-seq from control and KO livers to assess the transcriptional impact of the HNF1A upregulation in the Haster KO liver.
Source: GO:0060261
Synonyms:
- positive regulation of transcription initiation from RNA polymerase II promoter
Branch: biological process
Genes: Hnf1a (Mmu)...Hnf1a (Rno)...HNF1A (Hsa)
Tg(Hnf1a-RB1*)XMiu
(Mus musculus)Allele/Variant
Source: MGI:5312916
Genes: Not Available
Synonyms: Not Available
Variant Type: unreported
Molecular Consequence: Not Available
Diseases: Not Available
Variant Name: Not Available
Symbol: Tg(Hnf1a-RB1*)XMiu
Gene Ontology
Source: GO:0001221
Synonyms:
- RNA polymerase II transcription cofactor binding
- RNA polymerase II transcription coregulator binding
Branch: molecular function
Genes: Hnf1a (Mmu)...Hnf1a (Rno)
Model
Id: MGI:4942179
Synonyms: Not Available
Name: Tg(Ins2-Hnf1a)#Cbw/0 [background:] involves: C57BL/6 * CBA/J
Disease
Source: DOID:3526
Definition: A cerebrovascular disease that is characterized by an area of necrotic tissue in the brain resulting from a blockage or narrowing in the arteries supplying blood and oxygen to the brain.
Genes: hnf1a (Dre)...Hnf1a (Rno)...HNF1A (Hsa)...hnf1a (Xtr)...Hnf1a (Mmu)
Gene Ontology
Source: GO:0009749
Synonyms:
- response to glucose stimulus
Branch: biological process
Genes: Hnf1a (Rno)...HNF1A (Hsa)...Hnf1a (Mmu)
Gene Ontology
Source: GO:0032147
Synonyms:
- protein kinase activation
Branch: biological process
Genes: Hnf1a (Rno)
Gene Ontology
Source: GO:0001750
Synonyms: Not Available
Branch: cellular component
Genes: Hnf1a (Rno)...HNF1A (Hsa)...Hnf1a (Mmu)
Gene Ontology
Source: GO:0003323
Synonyms:
- pancreatic B cell development
- pancreatic beta cell development
Branch: biological process
Genes: hnf1a (Dre)
Disease
Source: DOID:557
Definition: A urinary system disease that is located_in the kidney.
Genes: hnf1a (Dre)...Hnf1a (Rno)...HNF1A (Hsa)...hnf1a (Xtr)...Hnf1a (Mmu)
Gene Ontology
Source: GO:0001223
Synonyms:
- RNA polymerase II transcription coactivator binding
Branch: molecular function
Genes: Hnf1a (Mmu)...Hnf1a (Rno)
Gene Ontology
Source: GO:0006633
Synonyms:
- fatty acid anabolism
- fatty acid biosynthesis
Branch: biological process
Genes: Hnf1a (Rno)...HNF1A (Hsa)...Hnf1a (Mmu)
Gene Ontology
Source: GO:0032024
Synonyms:
- activation of insulin secretion
- stimulation of insulin secretion
Branch: biological process
Genes: Hnf1a (Rno)...Hnf1a (Mmu)
Gene Ontology
Source: GO:0008203
Synonyms:
- cholesterol metabolism
Branch: biological process
Genes: Hnf1a (Rno)...HNF1A (Hsa)...Hnf1a (Mmu)
Gene Ontology
Source: GO:0001889
Synonyms: Not Available
Branch: biological process
Genes: hnf1a (Dre)...Hnf1a (Rno)...HNF1A (Hsa)...Hnf1a (Mmu)
Gene Ontology
Source: GO:0031018
Synonyms: Not Available
Branch: biological process
Genes: hnf1a (Dre)
Disease
Source: DOID:10591
Definition: A hypertension occurring during pregnancy characterized by large amounts of protein in the urine (proteinuria) and edema, usually by the last trimester of pregnancy.
Genes: HNF1A (Hsa)...hnf1a (Dre)...Hnf1a (Rno)...hnf1a (Xtr)...Hnf1a (Mmu)
Gene Ontology
Source: GO:0071333
Synonyms: Not Available
Branch: biological process
Genes: Hnf1a (Rno)...Hnf1a (Mmu)
Disease
Source: DOID:9352
Definition: A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin.
Genes: hnf1a.L (Xla)...Hnf1a (Rno)...hnf1a (Dre)...hnf1a (Xtr)...HNF1A (Hsa)
Alleles: Hnf1a
Gene Ontology
Source: GO:0046983
Synonyms: Not Available
Branch: molecular function
Genes: HNF1A (Hsa)...hnf1a (Dre)...Hnf1a (Rno)...Hnf1a (Mmu)
Enhancer grammar of liver cell types and hepatocyte zonation states [multiome_validation]
(Mus musculus)HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE236256
Tags: baseline
Summary: Cell type identity is encoded by gene regulatory networks (GRN), in which transcription factors (TFs) bind to enhancers to regulate target gene expression. In the mammalian liver, lineage TFs have been characterized for the main cell types, including hepatocytes. Hepatocytes cover a relatively broad cellular state space, as they differ significantly in their metabolic state, and function, depending on their position with respect to the central or portal vein in a liver lobule. It is unclear whether this spatially defined cellular state space, called zonation, is also governed by a well-defined gene regulatory code. To address this challenge, we have mapped enhancer-GRNs (eGRNs) across liver cell types at high resolution, using a combination of single-cell multi-omics, spatial omics, GRN inference, and deep learning. We found that zonated variation in gene expression in hepatocytes, liver sinusoidal endothelial cells and hepatocellular stellate cells corroborate cell state changes in transcription and chromatin accessibility with spatial transcriptomics. eGRN mapping suggests that zonation states in hepatocytes are driven by the repressors Tcf7l1 and Tbx3, that modulate the core hepatocyte GRN, controlled by Hnf4a, Cebpa, Hnf1a, Onecut1 and Foxa1, among others. To investigate how these TFs cooperate with cell type TFs, we performed an in vivo Massively Parallel Reporter Assay (MPRA) on 12,000 hepatocyte enhancers and used these data to train a hierarchical deep learning model (called DeepLiver) that exploits both enhancer accessibility and activity. DeepLiver confirms Cebpa, Onecut, Foxa1, Hnf1a and Hnf4a as drivers of enhancer specificity in hepatocytes; Tcf7l1/2 and Tbx3 as regulators of the zonation state; and Hnf4a, Hnf1a, AP-1 and Ets as activators. Finally, taking advantage of in silico mutagenesis predictions from DeepLiver and MPRA, we confirmed that the destruction of Tcf7l1/2 or Tbx3 motifs in zonated enhancers abrogates their zonation bias. Our study provides a multi-modal explanation of the regulatory code underlying hepatocyte identity and their zonation state, that can be exploited to engineer enhancers with desired activity levels and zonation patterns. 10x single cell multiome on the mouse liver
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE218468
Tags: baseline
Summary: Cell type identity is encoded by gene regulatory networks (GRN), in which transcription factors (TFs) bind to enhancers to regulate target gene expression. In the mammalian liver, lineage TFs have been characterized for the main cell types, including hepatocytes. Hepatocytes cover a relatively broad cellular state space, as they differ significantly in their metabolic state, and function, depending on their position with respect to the central or portal vein in a liver lobule. It is unclear whether this spatially defined cellular state space, called zonation, is also governed by a well-defined gene regulatory code. To address this challenge, we have mapped enhancer-GRNs (eGRNs) across liver cell types at high resolution, using a combination of single-cell multi-omics, spatial omics, GRN inference, and deep learning. We found that zonated variation in gene expression in hepatocytes, liver sinusoidal endothelial cells and hepatocellular stellate cells corroborate cell state changes in transcription and chromatin accessibility with spatial transcriptomics. eGRN mapping suggests that zonation states in hepatocytes are driven by the repressors Tcf7l1 and Tbx3, that modulate the core hepatocyte GRN, controlled by Hnf4a, Cebpa, Hnf1a, Onecut1 and Foxa1, among others. To investigate how these TFs cooperate with cell type TFs, we performed an in vivo Massively Parallel Reporter Assay (MPRA) on 12,000 hepatocyte enhancers and used these data to train a hierarchical deep learning model (called DeepLiver) that exploits both enhancer accessibility and activity. DeepLiver confirms Cebpa, Onecut, Foxa1, Hnf1a and Hnf4a as drivers of enhancer specificity in hepatocytes; Tcf7l1/2 and Tbx3 as regulators of the zonation state; and Hnf4a, Hnf1a, AP-1 and Ets as activators. Finally, taking advantage of in silico mutagenesis predictions from DeepLiver and MPRA, we confirmed that the destruction of Tcf7l1/2 or Tbx3 motifs in zonated enhancers abrogates their zonation bias. Our study provides a multi-modal explanation of the regulatory code underlying hepatocyte identity and their zonation state, that can be exploited to engineer enhancers with desired activity levels and zonation patterns. 10x single cell multiome on the mouse liver.
HTP Dataset Index
High-Throughput (HTP) Dataset Index metadata provided by MGI
ID: ArrayExpress:GSE218465
Tags: strain study, baseline
Summary: Cell type identity is encoded by gene regulatory networks (GRN), in which transcription factors (TFs) bind to enhancers to regulate target gene expression. In the mammalian liver, lineage TFs have been characterized for the main cell types, including hepatocytes. Hepatocytes cover a relatively broad cellular state space, as they differ significantly in their metabolic state, and function, depending on their position with respect to the central or portal vein in a liver lobule. It is unclear whether this spatially defined cellular state space, called zonation, is also governed by a well-defined gene regulatory code. To address this challenge, we have mapped enhancer-GRNs (eGRNs) across liver cell types at high resolution, using a combination of single-cell multi-omics, spatial omics, GRN inference, and deep learning. We found that zonated variation in gene expression in hepatocytes, liver sinusoidal endothelial cells and hepatocellular stellate cells corroborate cell state changes in transcription and chromatin accessibility with spatial transcriptomics. eGRN mapping suggests that zonation states in hepatocytes are driven by the repressors Tcf7l1 and Tbx3, that modulate the core hepatocyte GRN, controlled by Hnf4a, Cebpa, Hnf1a, Onecut1 and Foxa1, among others. To investigate how these TFs cooperate with cell type TFs, we performed an in vivo Massively Parallel Reporter Assay (MPRA) on 12,000 hepatocyte enhancers and used these data to train a hierarchical deep learning model (called DeepLiver) that exploits both enhancer accessibility and activity. DeepLiver confirms Cebpa, Onecut, Foxa1, Hnf1a and Hnf4a as drivers of enhancer specificity in hepatocytes; Tcf7l1/2 and Tbx3 as regulators of the zonation state; and Hnf4a, Hnf1a, AP-1 and Ets as activators. Finally, taking advantage of in silico mutagenesis predictions from DeepLiver and MPRA, we confirmed that the destruction of Tcf7l1/2 or Tbx3 motifs in zonated enhancers abrogates their zonation bias. Our study provides a multi-modal explanation of the regulatory code underlying hepatocyte identity and their zonation state, that can be exploited to engineer enhancers with desired activity levels and zonation patterns. 10x single cell multiome on the mouse liver.
Gene Ontology
Source: GO:0042593
Synonyms: Not Available
Branch: biological process
Genes: Hnf1a (Rno)...HNF1A (Hsa)...Hnf1a (Mmu)