Transcriptional and chromatin profiles of duodenum epithelium upon HNF4 loss in mice by RNA-seq and ChIP-seq
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE112946 | GEO | 2019/04/08
REPOSITORIES: GEO
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Project description:The goal of this study was to better understand the roles of Hnf4 fmaily transcription factors in zebrafish development and intestinal function. We used RNA-sequencing to compare gene expression changes in digestive tracts dissected from 6dpf larval zebrafish. Our first experiment compared samples from wild type and hnf4g-/- zebrafish which were either raised germ free or with a conventional microbiota starting at 3dpf. The second experiment compared samples from wild type, hnf4g-/-, and hnf4a-/-;hnf4g-/- zebrafish conventionally raised from 0dpf with a microbiota. Each sample consists of RNA extracted from 10-15 pooled gastrointestinal tracts, and 4 biological replicates per treatment group were sequenced.
2022-09-01 | GSE183799 | GEO
Project description:HNF4 paralogs are redundantly required for proper villus elongation, differentiation and maturation in the developing gut. We find 5,391 chromatin regions become inaccessible upon HNF4 loss, and HNF4 binding sequences are most enriched in these regions. Genes nearby these 5,391 HNF4 dependent regions are associated with villus differentiation/maturation.
2019-07-29 | GSE128674 | GEO
Project description:Background and Aims: HNF4a is a nuclear hormone receptor transcription factor that has been shown to be required for hepatocyte differentiation and development of the liver. It has also been implicated in regulating expression of genes that act in the epithelium of the lower gastrointestinal tract. This implied that HNF4a might be required for development of the gut. Methods: We generated mouse embryos in which HNF4a was ablated in the epithelial cells of the fetal colon using Cre-loxP technology. Embryos were examined using a combination of histology, immunohistochemistry, gene array and RT-PCR, and chromatin immunoprecipitation analyses to define the consequence of loss of HNF4a on colon development. Results: Embryos could be generated until E18.5 that lacked HNF4a in their colon. Although, early stages of colonic development occurred, HNF4a null colons failed to form normal crypts. In addition, goblet cell maturation was perturbed and expression of an array of genes that encode proteins with diverse roles in colon function was disrupted. Several genes whose expression in the colon was dependent on HNF4a contained HNF4a–binding sites sequences within putative transcriptional regulatory regions and a subset of these sites were occupied by HNF4a in vivo. Conclusion: HNF4a is a transcription factor that is essential for development of the mammalian colon, regulates goblet cell maturation and is required for expression of genes that control normal colon function and epithelial cell differentiation. Keywords: E18.5 FETAL HNF4 NULL COLONS
2006-01-01 | GSE3116 | GEO
Project description:To study the role of hepatic nuclear factor alpha (HNF4a in hepatogenesis, we used loxP-Cre technology to eliminate it from developing mouse livers. A comparison of control and experimental livers revealed that hepatocytes lacking HNF4a_failed to fully differentiate. Specifically, HNF4a null liver cells failed to express genes that are markers of mature hepatocytes including Gys2, Pck1, and G6pc. These cells also failed to form normal cellular junctions, which are critical for establishment of the hepatic epithelium [Parviz et al. (2003) Nat.Genet. 34, 292-96]. Because HNF4a functions as a transcription factor, we hypothesized that it regulates liver development by controlling the expression of genes whose products are essential in executing cellular differentiation and morphogenesis. To identify these genes, we compared expression profiles between HNF4a null and wild type E18.5 fetal livers using Affymetrix gene arrays. We identified 564 genes whose expression was decreased by at least 2.5-fold and 34 genes whose expression was increased by at least 2.5-fold when HNF4a was eliminated from hepatocytes. These represent genes involved in diverse molecular pathways, reflecting the pleiotropic phenotype of HNF4a null livers. Our goal was to use the information from the gene arrays to define the mechanisms through which HNF4a controls the generation of the hepatic epithelium. We identified 27 genes from our list of downregulated genes with either defined or predicted roles in cellular junctions and/or adhesion. Most striking was that loss of HNF4a altered the expression of genes encoding proteins involved in virtually all types of cellular junctions including tight junctions (Cldn1, Cldn-2, Cldn-12, Ocln, F11r/Jam1, Cxadr, Crb3), adherens junctions (Cdh1), desmosomes (Dsc2, Pkp2, Krt2-8), and gap junctions (Gjb1, Gjb2). Using immunoblotting and immunohistochemistry, we found that the expression of proteins representing each of these junction types was reduced or absent. Analysis of these genes for the presence of putative HNF4a binding sites revealed that 25 of 27 contain such sites. We have used chromatin immunoprecipitation to confirm that HNF4a occupies several of these sites in vivo, including Cdh1, Cldn1, and F11r/Jam1. From these data, we conclude that HNF4a is a central mediator of the fully differentiated hepatocyte gene expression program and that it orchestrates the expression of cell junction and adhesion proteins required for establishing the hepatic epithelium. Keywords: E18.5 fetal hnf4 null and control mouse livers
2005-12-31 | GSE3126 | GEO
Project description:Background and Aims: HNF4? is a nuclear hormone receptor transcription factor that has been shown to be required for hepatocyte differentiation and development of the liver. It has also been implicated in regulating expression of genes that act in the epithelium of the lower gastrointestinal tract. This implied that HNF4? might be required for development of the gut. Methods: We generated mouse embryos in which Hnf4? was ablated in the epithelial cells of the fetal colon using Cre-loxP technology. Embryos were examined using a combination of histology, immunohistochemistry, gene array and RT-PCR, and chromatin immunoprecipitation analyses to define the consequence of loss of HNF4? on colon development. Results: Embryos could be generated until E18.5 that lacked HNF4? in their colon. Although, early stages of colonic development occurred, HNF4? null colons failed to form normal crypts. In addition, goblet cell maturation was perturbed and expression of an array of genes that encode proteins with diverse roles in colon function was disrupted. Several genes whose expression in the colon was dependent on HNF4? contained HNF4?âbinding sites sequences within putative transcriptional regulatory regions and a subset of these sites were occupied by HNF4? in vivo. Conclusion: HNF4? is a transcription factor that is essential for development of the mammalian colon, regulates goblet cell maturation and is required for expression of genes that control normal colon function and epithelial cell differentiation. Experiment Overall Design: COMPARISON OF 3 MUTANT TO 2 CONTROL COLONS.
2008-06-12 | E-GEOD-3116 | biostudies-arrayexpress
Project description:To define changes in gene expression resulting from loss of hnf4 in the small intestine. Keywords: genetic modification
2005-12-31 | GSE3124 | GEO
Project description:This study provides a map of enhancer-promoter interactions in the intestinal epithelium. We find that key drivers of intestinal differentiation, HNF4 transcription factors, are required for enhancer-promoter interactions at their direct target genes. Depletion of HNF4 disrupts chromatin looping, nearby enhancer chromatin, and target gene expression.
2021-01-16 | GSE148691 | GEO
Project description:We performed bulk RNA-seq and compared complehensive gene expression profiles of kidney organoids induced from wild type, HNF4A-KO, HNF4G-KO, and HNF4A/4G-DKO iPS cell lines.
2023-10-23 | GSE226439 | GEO
Project description:The mechanisms driving gene expression changes during intestinal differentiation are unclear. Our studies have shown differential recruitment and occupancy of Pol II to be a major driver of these gene expression changes. Additionally, we have identified the transcription factor HNF4 as a key player in shaping this phenomenon. To gain insights into the protein-based mechanisms underlying HNF4-mediated Pol II recruitment, we performed RIME (Rapid Immunoprecipitation Mass Spectrometry of Endogenous proteins) using anti-HNF4A antibodies in primary mouse epithelium.
2023-10-09 | MSV000093071 | MassIVE
Project description:Although mutations in the nuclear receptor HNF4A were identified as the cause of Maturity Onset Diabetes of the Young 1 (MODY1) nearly two decades ago, the mechanisms by which HNF4A regulates glucose homeostasis remain unclear. Here we report that loss of Drosophila HNF4 recapitulates hallmark symptoms of MODY1, including adult-onset hyperglycemia, glucose intolerance and impaired glucose-stimulated insulin secretion (GSIS). These defects are linked to an unexpected role for dHNF4 within mitochondria to directly regulate mtDNA transcription, while also promoting the expression of nuclear genes involved in oxidative phosphorylation (OXPHOS) and Hex-C, a homolog of the MODY2 gene Glucokinase. dHNF4 is required in the fat body and insulin-producing cells to maintain glucose homeostasis by supporting a developmental switch toward OXPHOS and GSIS at the transition to adulthood. These findings establish an animal model for MODY1 and define a developmental reprogramming of metabolism to support the energetic needs of the mature animal.
2015-11-28 | GSE73675 | GEO