Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hepatocyte Nuclear Factor 1 coordinates multiple functions of intestinal epithelial cells

ABSTRACT: Background and Aims: Hepatocyte nuclear factor 1 (HNF1) transcription factors direct tissue specific gene regulation in liver, pancreas and kidney and are associated with diabetes. Here we investigate the transcriptional network governed by HNF1 in an intestinal epithelial cell line. Methods: Chromatin immunoprecipitation followed by direct sequencing (ChIP-seq) was used to identify HNF1 binding sites genome-wide. Direct targets of HNF1 were validated using conventional ChIP assays. siRNA-mediated depletion of HNF1 followed by RT-qPCR further confirmed target genes. The effect of HNF1 reduction on glucose uptake was measured by fluorescence activated cell sorting (FACS) following treatment of intestinal epithelial cells with 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG, a fluorescent glucose mimic). Results: HNF1 controls multiple pathways that are critical for intestinal epithelial cell function, including properties of the cell membrane, cellular response to hormones, and regulation of biosynthetic processes. Approximately 50% of HNF1 binding sites are also occupied by hepatocyte nuclear factor 4A (HNF4A), caudal type homeobox 2 (CDX2), and forkhead box A2 (FOXA2). Depletion of HNF1 increases FOXA2 abundance and decreases levels of CDX2. Moreover, loss of HNF1 inhibits glucose uptake by the intestinal epithelial cell line. Conclusions: These data show that HNF1 plays a critical role in regulating intestinal epithelial cell functions including glucose absorption. HNF1 interacts with other tissue-specific transcription factors to regulate differentiated properties of these cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE67740 | GEO | 2016/10/09

SECONDARY ACCESSION(S): PRJNA280810

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

HNF-1alpha Triggers Initiation of the Human Intestinal Cell Differentiation Program in Cooperation with Cdx-2 and GATA-4

Project description:Transcriptional profiling of undifferentiated HIEC cells stably infected with a retroviral inducible expression vector (RevTet system) comparing DOX-induced HIEC pTetON with DOX-induced HIEC cells expressing either HNF1 and CDX2 or HNF1, CDX2 plus GATA4. Keywords: Differential gene expression Three-condition experiment, DOX-induced HIEC expressing HNF1-CDX2 vs DOX-induced HIEC pTetON, DOX-induced HIEC expressing HNF1-CDX2 plus GATA4 vs DOX-induced HIEC pTetON.

2010-01-28 | E-GEOD-11421 | biostudies-arrayexpress

HNF-1alpha Triggers Initiation of the Human Intestinal Cell Differentiation Program in Cooperation with Cdx-2 and GATA-4

2010-01-29 | GSE11421 | GEO

Distinct processes and transcriptional targets underlie CDX2 requirements in intestinal stem cells and differentiated villus cells

Project description:To define target genes of the intestine-restricted transcription factor (TF) CDX2 in intestinal stem cells, we performed chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq). We used RNA-sequencing to profile gene expression changes during cell differentiation from mouse intestinal stem cells to mature villus cells, as well as genes perturbed in intestinal stem cells upon loss of Cdx2. We find thousands of genes that change in expression during cell differentiation, including known stem cell and mature markers. Upon loss of Cdx2, hundreds of genes are up and down-regulated in intestinal stem cells, some of which are also bound by CDX2 nearby and constitute candidate direct target genes. CDX2 ChIP-Seq analysis of isolated mouse intestinal stem cells. RNA seq analysis of control mouse villus cells, control intestinal stem cells and Cdx2-deleted intestinal stem cells.

2015-09-15 | E-GEOD-70766 | biostudies-arrayexpress

Distinct processes and transcriptional targets underlie CDX2 requirements in intestinal stem cells and differentiated villus cells

2015-09-15 | GSE70766 | GEO

FOXA2 regulates a network of genes involved in critical functions of intestinal epithelia

Project description:Background and Aims: The forkhead box A (FOXA) family of pioneer transcription factors is critical for the development of many endoderm-derived tissues including the lung and the liver. Here we investigate the role of FOXA2 in regulating intestinal epithelial cell function. Methods: ChIP-seq was used to identify FOXA2 binding sites genome-wide. Targets of FOXA2 were validated using ChIP-qPCR and siRNA-mediated depletion of FOXA1/2 followed by RT-qPCR. A luciferase-based assay was used to measure intracellular cAMP after FOXA1/2 modulation.Results: Peaks of FOXA2 occupancy were frequent at loci contributing to gene ontology pathways of regulation of cell migration, cell motion, and plasma membrane function. Depletion of both FOXA1 and FOXA2 led to a significant reduction in the expression of multiple transmembrane proteins including ion transporters. One of the targets was the adenosine A2B receptor, and reduced receptor mRNA levels were associated with a functional decrease in intracellular cAMP. We also observed that 30% of FOXA2 binding sites contained a GATA motif and that FOXA1/A2 depletion reduced GATA-4, but not GATA-6 protein levels. Conclusions: These data show that FOXA2 plays a critical role in regulating intestinal epithelial cell function. FOXA2 depletion affects the expression of ion transporters and other transmembrane proteins, which form a network essential for maintaining normal ion and solute transport. Moreover, we show that the FOXA and GATA families of transcription factors may work cooperatively to regulate gene expression genome-wide. To determine the role of FOXA2 in regulating gene expression in intestinal epithelial cells, ChIP-seq was performed for FOXA2 in Caco2 (colorectal adenocarcinoma) cells.

2015-08-06 | E-GEOD-66218 | biostudies-arrayexpress

Transcription profiling of mouse early endoderm from wild type and homeobox transcription factor Cdx2 knock-out strains

Project description:We demonstrate that conditional ablation of the homeobox transcription factor Cdx2 from early endoderm results in the replacement of the posterior intestinal epithelium with keratinocytes, a dramatic cell fate conversion caused by ectopic activation of the foregut/esophageal differentiation program. This anterior homeotic transformation is first evident in the early embryonic Cdx2-deficient gut as expression of several key foregut endoderm regulators was shifted caudally. While the intestinal transcriptome was severely affected, Cdx2-deficiency only transiently modified selected posterior Hox genes and the primary enteric Hox code was maintained. Further, we demonstrate that Cdx2-directed intestinal cell fate adoption plays an important role in the establishment of normal epithelial-mesenchymal interactions, as multiple signaling pathways involved in this process were severely affected. We conclude that Cdx2 controls important aspects of intestinal identity and development, and that this function is largely independent of the enteric Hox code. Gene ablation was achieved by creating a Cdx2 loxP/loxP mouse which was then crossed with a Foxa3-CRE mouse to yield Cdx2 loxP/loxP Foxa3-CRE mice.

2009-03-19 | E-MTAB-92 | biostudies-arrayexpress

Histone methylation and transcription factor binding during intestinal cell differentation

Project description:Cell differentiation requires epigenetic modulation of tissue-specific genes and activities of master transcriptional regulators, which are recognized for their dominant control over cellular programs. Using novel epigenomic methods, we characterized enhancer elements specifically modified in differentiating intestinal epithelial cells and found enrichment of transcription factor-binding motifs corresponding to CDX2, a master regulator of the intestine. Directed investigation revealed surprising lability in CDX2 occupancy of the genome, with redistribution from hundreds of sites occupied only in progenitors to thousands of new sites in mature cells. Knockout mice confirmed distinct Cdx2 requirements in dividing and differentiated adult intestinal cells, including responsibility for the active enhancer configuration associated with maturity. Dynamic CDX2 occupancy corresponds with condition-specific gene expression and, importantly, to differential co-occupancy with other tissue-restricted transcription factors: HNF4A in mature cells and GATA6 in progenitors. These results reveal dynamic, context-specific functions and mechanisms of a master transcription factor within a cell lineage. H3K4me2, CDX2, GATA6, and HNF4A ChIP-seq patterns were mapped in proliferating and 26 day post-confluent (differentatied) Caco-2 intestinal cell lines and compared to published expression data or newly generated Cdx2 knockout mouse intestine expression data

2010-11-17 | E-GEOD-23436 | biostudies-arrayexpress

Loss of Hepatocyte-Nuclear-Factor-1α Impacts on Adult Mouse Intestinal Epithelial Cell Growth and Cell Lineages Differentiation

Project description:Although hepatocyte-nuclear-factor-1α (Hnf1α) is crucial for pancreas and liver functions, it is believed to play a limited functional role for intestinal epithelial functions. The aim of this study was to assess the consequences of abrogating Hnf1α on the maintenance of adult small intestinal epithelial functions. Methodology/Principal Findings An Hnf1α knockout mouse model was used. Assessment of histological abnormalities, crypt epithelial cell proliferation, epithelial barrier, glucose transport and signalling pathways were measured in these animals. Changes in global gene expression were also analyzed. Mice lacking Hnf1α displayed increased crypt proliferation and intestinalomegaly as well as a disturbance of intestinal epithelial cell lineages production during adult life. This phenotype was associated with a decrease of the mucosal barrier function and lumen-to-blood glucose delivery. The mammalian target of rapamycin (mTOR) signalling pathway was found to be overly activated in the small intestine of adult Hnf1α mutant mice. The intestinal epithelium of Hnf1α null mice displayed a reduction of the enteroendocrine cell population. An impact was also observed on proper Paneth cell differentiation with abnormalities in the granule exocytosis pathway. Conclusions/Significance Together, these results unravel a functional role for Hnf1α in regulating adult intestinal growth and sustaining the functions of intestinal epithelial cell lineages. HNF1alpha was knocked out. A total of 3 control and 3 mutant littermate individuals were sacrificed at 4 months of age. The jejunum was harvested and total RNA was isolated from each individual. Each RNA sample was independently used to generate probes to screen Affymetrix chips.

2011-01-01 | E-GEOD-23040 | biostudies-arrayexpress

COLO320 cells: siCDX2 vs. non-targeting control

Project description:Somatic DNA alteration underlies tumor development and progression, and gives rise to tumors with diverse genetic contexts. Here, we identify in a collection of 29 colorectal cancer cell lines and 226 primary colorectal tumors recurrent amplification of chromosome 13, an alteration highly restricted to colorectal-derived cancers. A minimal region of amplification on 13q12.2 pinpoints caudal type homeobox transcription factor CDX2, a master regulator of anterior-posterior patterning, midgut development, and intestinal epithelial cell differentiation and maintenance. In contrast to its described role as a colorectal tumor suppressor, we show that in the context of genomic amplification, CDX2 is required for proliferation and anchorage-independent growth of colorectal cancer cells. By genome-wide expression and location analysis, we reveal that CDX2 directly promotes expression of Wnt pathway genes. Further results suggest that CDX2 induces expression of intestinal differentiation markers and modulates b-catenin transcriptional activity. These data characterize CDX2 as a novel lineage-survival oncogene deregulated in colorectal cancer. Two-condition experiment, CDX2 siRNA knockdown vs. control, using two independent siRNAs against CDX2

2012-11-02 | E-GEOD-30181 | biostudies-arrayexpress

Colorectal Cancer Cell Lines aCGH

2012-11-02 | E-GEOD-29953 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data