The Nucleosome Map of the Mammalian Liver
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE26729 | GEO | 2011/04/30
SECONDARY ACCESSION(S): PRJNA136145
REPOSITORIES: GEO
Similar Datasets
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
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
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. 5 biological replicates examined
2012-06-21 | E-GEOD-33666 | biostudies-arrayexpress
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
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
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.
2015-08-06 | GSE66218 | GEO
Project description:Mapping of cohesin, CTCF and a collection of tissue-specific and ubiquitous transcriptional regulators using ChIP-seq in primary mouse liver. The following antibodies were used: CTCF (upstate, 07729), STAG1 (abcam, ab4457), STAG2 (abcam, 4464), RAD21 (abcam, ab992), CEBPA (santa cruz, sc9314), HNF4A (aviva systems biology, ARP31946), FOXA1 (abcam, ab5089), FOXA2 (santa cruz, sc6554), HNF6 (santa cruz, sc13050), HNF1A (santa cruz, sc6547), PREP1 (santa cruz, sc6245), NRSF/REST (santa cruz, sc25398), GABPA (santa cruz, sc22810), E2F4 (santa cruz, sc1082), p300 (santa cruz, sc585), CBP (santa cruz, sc369), RNAP2 (abcam, ab5408), H3K4me1 (abcam, ab8895), H3K4me3 (abcam, ab8580), H3K36me3 (abcam, ab9050), H3K79me2 (abcam, ab3594), H2AK5ac (abcam, 1764)
2012-06-22 | E-MTAB-941 | biostudies-arrayexpress
Project description:Triglyceride accumulation in nonalcoholic fatty liver (NAFL) results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox) transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2, however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB). Moreover, Foxa1 represses the fatty acid transporter FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing HMGCS2 and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolism pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance. To determine the global impact of Foxa1 on human liver gene transcription, microarray expression analyses were performed in HepG2 cells transfected with Ad-Foxa1 or Ad-Control. We used microarrays to detail the global programme of gene expression in HepG2 cells infected with Ad-Foxa1 or control adenovirus (insertless Ad-pACC).
2011-07-07 | E-GEOD-30447 | biostudies-arrayexpress
Project description:Triglyceride accumulation in nonalcoholic fatty liver (NAFL) results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox) transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2, however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB). Moreover, Foxa1 represses the fatty acid transporter FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing HMGCS2 and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolism pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance. To determine the global impact of Foxa1 on human liver gene transcription, microarray expression analyses were performed in human hepatocytes transfected with Ad-Foxa1 or Ad-Control. We used microarrays to detail the global programme of gene expression in human hepatocytes infected with Ad-Foxa1 or control adenovirus (insertless Ad-pACC).
2011-07-07 | E-GEOD-30450 | biostudies-arrayexpress
Project description:Gene expression changes between livers of treated WT and dKO (Foxa1 and Foxa2 KO) male and female mice and untreated female (WT and dKO) mice were measured to identify pathways related to Foxa1/2 regulation of pathways involved in liver cancer. The experiment uses 4 replicates each for 6 conditions
2012-01-20 | E-GEOD-32244 | biostudies-arrayexpress