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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide location analysis of Foxa1 in adult liver

ABSTRACT: We determine by genome-wide location analysis (ChIP-Seq) that Foxa1 occupies 5,682 binding sites in the adult murine liver. Although Foxa1 and its closest paralog Foxa2 (GEO accessions: GSE25836 and GSE26729) share a large fraction of binding sites in the liver, each protein also occupies distinct regulatory elements in vivo. Foxa1-only sites have a weaker forkhead motif are enriched for p53 binding sites and are frequently found near genes important to cell cycle regulation, while Foxa2-restricted sites show only a stronger match to the forkhead consensus and are found in genes involved in steroid and lipid metabolism. Thus, Foxa1 and Foxa2, while redundant during development, have evolved divergent roles in the adult liver, ensuring the maintenance of both genes during evolution. 5 biological replicates examined

ORGANISM(S): Mus musculus

SUBMITTER: Irina Bochkis

PROVIDER: E-GEOD-33666 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Genome-wide location analysis reveals distinct transcriptional circuitry by paralogous regulators Foxa1 and Foxa2.

Bochkis Irina M IM Schug Jonathan J Ye Diana Z DZ Kurinna Svitlana S Stratton Sabrina A SA Barton Michelle C MC Kaestner Klaus H KH

PLoS genetics 20120621 6

Gene duplication is a powerful driver of evolution. Newly duplicated genes acquire new roles that are relevant to fitness, or they will be lost over time. A potential path to functional relevance is mutation of the coding sequence leading to the acquisition of novel biochemical properties, as analyzed here for the highly homologous paralogs Foxa1 and Foxa2 transcriptional regulators. We determine by genome-wide location analysis (ChIP-Seq) that, although Foxa1 and Foxa2 share a large fraction of ...[more]

PMID: 22737085

Similar Datasets

Genome-wide location analysis of Foxa1 in adult liver

Project description:We determine by genome-wide location analysis (ChIP-Seq) that Foxa1 occupies 5,682 binding sites in the adult murine liver. Although Foxa1 and its closest paralog Foxa2 (GEO accessions: GSE25836 and GSE26729) share a large fraction of binding sites in the liver, each protein also occupies distinct regulatory elements in vivo. Foxa1-only sites have a weaker forkhead motif are enriched for p53 binding sites and are frequently found near genes important to cell cycle regulation, while Foxa2-restricted sites show only a stronger match to the forkhead consensus and are found in genes involved in steroid and lipid metabolism. Thus, Foxa1 and Foxa2, while redundant during development, have evolved divergent roles in the adult liver, ensuring the maintenance of both genes during evolution.

2012-06-21 | GSE33666 | GEO

The Nucleosome Map of the Mammalian Liver

Project description:We report the genome-wide map of nucleosome positions in the mouse liver, with emphasis on transcriptional start sites, CpG islands, Foxa2 binding sites, and their correlation with gene expression. Despite the heterogeneity of liver tissue, we could clearly discern the nucleosome pattern of the predominant liver cell, the hepatocyte. By analyzing nucleosome occupancy and the distributions of heterochromatin protein 1 (Hp1), CBP, and p300 in Foxa1/2-deficient livers we find, surprisingly, that the maintenance of nucleosome position and chromatin structure surrounding Foxa2 binding sites is independent of Foxa1/2. Examination of nucleosome map and Foxa2 binding in the mouse liver.

2011-04-30 | E-GEOD-26729 | biostudies-arrayexpress

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

The Nucleosome Map of the Mammalian Liver

Project description:Mammalian genomes contain billions of basepairs of DNA that must be highly compacted as chromatin to fit into the nano-scale of the nucleus, but yet be accessible to allow for transcription to occur. Binding to nucleosomal DNA is critical for ÔpioneerÕ transcription factors such as Foxa1 and Foxa2 to regulate chromatin structure and gene activation. Here we report the genome-wide map of nucleosome positions in the mouse liver, with emphasis on transcriptional start sites, CpG islands, Foxa2 binding sites, and their correlation with gene expression. Despite the heterogeneity of liver tissue, we could clearly discern the nucleosome pattern of the predominant liver cell, the hepatocyte. By analyzing nucleosome occupancy and the distributions of heterochromatin protein 1 (Hp1), CBP, and p300 in Foxa1/2-deficient livers we find, surprisingly, that the maintenance of nucleosome position and chromatin structure surrounding Foxa2 binding sites is independent of Foxa1/2. Original data matrix is in the archive: E-MTAB-514.additional.zip

2011-05-05 | E-MTAB-514 | biostudies-arrayexpress

The Nucleosome Map of the Mammalian Liver

2011-04-30 | GSE26729 | GEO

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

2015-08-06 | GSE66218 | GEO

Changes in nucleosome occupancy associated with metabolic alterations in aged mammalian liver [ChIP-seq]

Project description:Aging is accompanied by physiological impairments, which, in insulin-responsive tissues, including the liver, predispose individuals to metabolic disease. However, the molecular mechanisms underlying these changes remain largely unknown. Here, we analyze genome-wide profiles of RNA and chromatin organization in the liver of young (3 months) and old (21 months) mice. Transcriptional changes suggest that de-repression of the nuclear receptors PPARα, PPARγ, and LXRα in aged mouse liver leads to activation of targets regulating lipid synthesis and storage, whereas age-dependent changes in nucleosome occupancy are associated with binding sites for both known regulators (forkhead factors and nuclear receptors) and for novel candidates associated with nuclear lamina (Hdac3 and Srf) implicated to govern metabolic function of aging liver. Winged-helix factor Foxa2 and nuclear receptor co-repressor Hdac3 exhibit reciprocal binding pattern at PPARα targets contributing to gene expression changes that lead to steatosis in aged liver. Genome-wide location analysis (ChIP-Seq) of Foxa2 and Hdac3 from young (3 months) and old (21 months) mouse livers

2014-10-23 | E-GEOD-60393 | biostudies-arrayexpress

Nucleosome occupancy profiles in young and old mouse liver [MNase-Seq]

Project description:Aging is accompanied by physiological impairments, which, in insulin-responsive tissues, including the liver, predispose individuals to metabolic disease. However, the molecular mechanisms underlying these changes remain largely unknown. Here, we analyze genome-wide profiles of RNA and chromatin organization in the liver of young (3 months) and old (21 months) mice. Transcriptional changes suggest that de-repression of the nuclear receptors PPARM-NM-1, PPARM-NM-3, and LXRM-NM-1 in aged mouse liver leads to activation of targets regulating lipid synthesis and storage, whereas age-dependent changes in nucleosome occupancy are associated with binding sites for both known regulators (forkhead factors and nuclear receptors) and for novel candidates associated with nuclear lamina (Hdac3 and Srf) implicated to govern metabolic function of aging liver. Winged-helix factor Foxa2 and nuclear receptor co-repressor Hdac3 exhibit reciprocal binding pattern at PPARM-NM-1 targets contributing to gene expression changes that lead to steatosis in aged liver. Genome-wide nucleosome profiles (MNase-Seq) from young (3 months) and old (21 months) mouse livers

2014-10-23 | E-GEOD-58005 | biostudies-arrayexpress

Analysis of the impact of FOXA1 expression on MDA::ER E2-sensitive transcriptomes and ER cistromes [Transcriptome data]

Project description:The primordial actions of the estrogen receptor alpha (ER) in controlling breast cancer cells proliferation rate are particularly documented. However, reintroducing ER into ER-negative cells does not reprogram their transcriptome towards an estrogen-sensitive growth phenotype. Member of the Forkhead (FKH) family of transcription factors, FOXA1 has been characterized to be essential for the appropriate binding of ER onto chromatin in MCF-7 cells. FOXA1 pioneering actions involve modulations of histone post-translational modifications (HPTMs) and local depletion in methylated CpGs. Using MDA-MB231 cells which are ER and FOXA1 negative, we aimed at determining whether the introduction of ER and FOXA1 would be sufficient to restore an estrogen-sensitive growth and to coincidently reprogram chromatin. We used ChIP-seq experiments to map ER and FOXA1 binding sites (BSs) and to profile H3K4me2 and H3K27ac marks, and surprisingly observed that FOXA1 had rather a global negative impact on ER actions, associated with an inhibition of growth and a reorientation of the transcriptome of the cells towards cell death. We demonstrate that the re-introduction of FOXA1 in these cells actually competes for the binding and pioneering actions of FOXA2, another FKH protein, on a number of ER BSs. As demonstrated for its alter ego FOXA1 in MCF-7 cells, abrogating FOXA2 expression drastically diminished ER binding onto its cognate sites, associated with a local loss of HPTMs for active chromatin.

2022-12-11 | GSE55680 | GEO

Analysis of the impact of FOXA1 expression on MDA::ER E2-sensitive transcriptomes and ER cistromes [ChIP-Seq data]

2022-12-11 | GSE55740 | GEO

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