Identification of Hnf6 binding sites in male and female mouse liver
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE60014 | GEO | 2015/07/28
SECONDARY ACCESSION(S): PRJNA257278
REPOSITORIES: GEO
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Project description:∼40,000 HNF6 binding sites were identified in mouse liver chromatin, including several thousand sites showing significant differences in level of HNF6 binding between male and female mouse liver. These sex-biased HNF6 binding sites showed strong enrichment for sex-biased DNase hypersensitive sites and for proximity to genes showing local sex-biased chromatin marks and a corresponding sex-biased expression. ~90% of genome-wide CUX2 binding sites identified previously in female mouse liver (Conforto TL, Zhang Y, Sherman J, Waxman DJ., Mol Cell Biol. 2012;32(22):4611-4627) were also bound by HNF6, giving evidence for genome-wide competition between HNF6 and CUX2 for chromatin binding in female mouse liver. These HNF6/CUX2 common binding sites were enriched for genomic regions more accessible in male than in female mouse liver chromatin, and showed strongest enrichment for male-biased genes, suggesting HNF6 displacement by CUX2 as a mechanism to explain the observed CUX2 repression of male-biased genes in female liver. However, HNF6 binding was sex-independent at a majority of its binding sites, and peak regions of HNF6 binding were frequently associated with co-binding by multiple other liver transcription factors, consistent with HNF6 playing a global regulatory role in both male and female liver. Livers were excised from individual male and female mice, cross-linked and sonicated, then used to identify HNF6 binding sites by ChIP-Seq using antibody specific to HNF6 (sc-13050; Santa Cruz Biotechnology, Inc).
2015-07-28 | E-GEOD-60014 | biostudies-arrayexpress
Project description:Growth hormone (GH)-regulated transcription factors, notably STAT5 and BCL6, play a major role in regulating genes showing sex differences in expression in mouse liver, primarily through their effects in male liver, where male-biased genes are up regulated and many female-biased genes are actively repressed. Here we investigate whether complementary mechanisms, involving up regulation of female-biased genes and down regulation of male-biased genes occur in female liver. To address this question, we identified genes regulated by Cux2, a highly female-specific transcription factor that is repressed in male liver and is induced by the female plasma GH pattern in female liver. ChIP-seq analysis identified Cux2 binding sites in female liver only, where they are enriched at sites of male-biased DNase hypersensitivity and at genomic regions showing male-enriched STAT5 binding. Cux2 binding sites were enriched at genes repressed by adenoviral-Cux2, but not at genes induced by adenoviral-Cux2 (see GSE35897), indicating a direct binding mechanism in Cux2 repression but not in Cux2-dependent gene induction. (Published in: TL Conforto et al 2012, Mol Cell Biol. 2012, 32:4611-4627. PubMed PMID: 22966202; PMCID: PMC3486175) Mouse livers were excised from individual male and female. Sonicated, cross-linked liver nuclear chromatin was then used to identify Cux2 binding sites by ChIP-Seq using antibody specific to Cux2, amino acids 356 to 415
2012-09-10 | E-GEOD-35985 | biostudies-arrayexpress
Project description:Growth hormone (GH)-regulated transcription factors, notably STAT5 and BCL6, play a major role in regulating genes showing sex differences in expression in mouse liver, primarily through their effects in male liver, where male-biased genes are up regulated and many female-biased genes are actively repressed. Here we investigate whether complementary mechanisms, involving up regulation of female-biased genes and down regulation of male-biased genes occur in female liver. To address this question, we identified genes regulated by Cux2, a highly female-specific transcription factor that is repressed in male liver and is induced by the female plasma GH pattern in female liver. ChIP-seq analysis identified Cux2 binding sites in female liver only, where they are enriched at sites of male-biased DNase hypersensitivity and at genomic regions showing male-enriched STAT5 binding. Cux2 binding sites were enriched at genes repressed by adenoviral-Cux2, but not at genes induced by adenoviral-Cux2 (see GSE35897), indicating a direct binding mechanism in Cux2 repression but not in Cux2-dependent gene induction. (Published in: TL Conforto et al 2012, Mol Cell Biol. 2012, 32:4611-4627. PubMed PMID: 22966202; PMCID: PMC3486175)
2012-09-10 | GSE35985 | GEO
Project description:We identified genes expressed in mouse liver that are regulated by Cux2, a highly female-specific liver transcription factor whose expression is regulated by sex-dependent plasma GH patterns. Using adenovirus to overexpress Cux2 (Adeno-Cux2) in male liver, we show that Cux2 represses ~35% of male-biased genes and induces/de-represses ~35% of female-biased genes. Adeno-CMV was used as a control for adenoviral infection. (Published in: TL Conforto et al 2012, Mol Cell Biol. 2012, 32:4611-4627. PubMed PMID: 22966202; PMCID: PMC3486175)
2012-09-10 | GSE35897 | GEO
Project description:We identified genes expressed in mouse liver that are regulated by Cux2, a highly female-specific liver transcription factor whose expression is regulated by sex-dependent plasma GH patterns. Using siRNA to knockdown Cux2 expression in female liver, we show that female specific genes are predominantly repressed by Cux2 knockdown. In contrast, similar numbers of male-biased genes are repressed as are induced by Cux2 knockdown. A scrambled, non-specific siRNA was used as a control. (Published in: TL Conforto et al 2012, Mol Cell Biol. 2012, 32:4611-4627. PubMed PMID: 22966202; PMCID: PMC3486175)
2012-09-10 | GSE37078 | GEO
Project description:Here we map six chromatin modifications -- H3K4me1, H3K4me3, H3K27ac, H3K36me3, H3K9me3, and H3K27me3 -- genome-wide in male and female mouse liver in order to identify histone modifications that characterize sex-biased genes and sex-biased DNase hypersensitive sites and their regulation by plasma growth hormone (GH) profiles, which are sexually dimorphic. We find distinct mechanisms of regulation in male liver and female liver: sex-dependent K27me3-mediated repression is an important mechanism of repression of female-biased, but not of male-biased, genes, and a sex-dependent K4me1 distribution, suggesting nucleosome repositioning by pioneer factors, is observed at male-biased, but not female-biased, regulatory sites. STAT5-mediated activation is most strongly associated with sex-biased chromatin modifications, while BCL6-mediated repression primarily occurs in association with sex-independent chromatin modifications, both at binding sites and at target genes. These samples are part of a study on chromatin states in male and female mouse and their role in sex-biased liver gene expression (A Sugathan and DJ Waxman (2013) Molec Cell Biol).
2013-07-03 | GSE44571 | GEO
Project description:Sex-dependent pituitary growth hormone (GH) secretory patterns determine the sex-biased expression of >1,000 genes in mouse and rat liver, affecting lipid and drug metabolism, inflammation and disease. A fundamental biological question is how robust differential expression can be achieved for hundreds of sex-biased genes simply based on the GH input signal pattern: pulsatile GH stimulation in males vs. near-continuous GH exposure in females. STAT5 is an essential transcriptional mediator of the sex-dependent effects of GH in the liver, but the mechanisms that underlie its sex-dependent actions are obscure. Here we elucidate the dynamic, sex-dependent binding of STAT5 and the GH/STAT5-regulated repressor BCL6 to mouse liver chromatin, revealing the counteractive interplay between these two regulators of liver sex-specificity. Our findings establish a close correlation between sex-dependent STAT5 binding and sex-biased target gene expression. Moreover, sex-dependent STAT5 binding correlated positively with sex-biased DNase hypersensitivity and H3-K4me1 and H3-K4me3 (activating) marks, correlated negatively with sex-biased H3-K27me3 (repressive) marks, and was associated with sex-differentially enriched motifs for HNF6/CDP factors. Importantly, BCL6 binding was preferentially associated with repression of female-biased STAT5 targets in male liver. Furthermore, BCL6 and STAT5 common targets but not BCL6 unique targets showed strong enrichment for lipid and drug metabolism. These findings provide a comprehensive, genome-wide view of the mechanisms whereby these two GH-regulated transcription factors establish and maintain sex differences affecting liver physiology and disease. The approaches used here to characterize sex-dependent STAT5 and BCL6 binding can be applied to other condition-specific regulatory factors and binding sites and their interplay with co-operative chromatin-binding factors. Mouse livers were excised from individual male and female mice killed at either a peak of STAT5 binding activity, or during the growth hormone (GH) interpulse interval, when STAT5 activity is either low (females) or essentially undetectable (males). Sonicated, cross-linked liver nuclear chromatin was then used to identify STAT5 binding sites by ChIP-Seq.
2011-12-18 | E-GEOD-31578 | biostudies-arrayexpress
Project description:Here we map six chromatin modifications -- H3K4me1, H3K4me3, H3K27ac, H3K36me3, H3K9me3, and H3K27me3 -- genome-wide in male and female mouse liver in order to identify histone modifications that characterize sex-biased genes and sex-biased DNase hypersensitive sites and their regulation by plasma growth hormone (GH) profiles, which are sexually dimorphic. We find distinct mechanisms of regulation in male liver and female liver: sex-dependent K27me3-mediated repression is an important mechanism of repression of female-biased, but not of male-biased, genes, and a sex-dependent K4me1 distribution, suggesting nucleosome repositioning by pioneer factors, is observed at male-biased, but not female-biased, regulatory sites. STAT5-mediated activation is most strongly associated with sex-biased chromatin modifications, while BCL6-mediated repression primarily occurs in association with sex-independent chromatin modifications, both at binding sites and at target genes. These samples are part of a study on chromatin states in male and female mouse and their role in sex-biased liver gene expression (A Sugathan and DJ Waxman (2013) Molec Cell Biol). Examination of six different histone modifications in male and female mouse liver.
2013-07-03 | E-GEOD-44571 | biostudies-arrayexpress
Project description:Sex-dependent pituitary growth hormone (GH) secretory patterns determine the sex-biased expression of >1,000 genes in mouse and rat liver, affecting lipid and drug metabolism, inflammation and disease. A fundamental biological question is how robust differential expression can be achieved for hundreds of sex-biased genes simply based on the GH input signal pattern: pulsatile GH stimulation in males vs. near-continuous GH exposure in females. STAT5 is an essential transcriptional mediator of the sex-dependent effects of GH in the liver, but the mechanisms that underlie its sex-dependent actions are obscure. Here we elucidate the dynamic, sex-dependent binding of STAT5 and the GH/STAT5-regulated repressor BCL6 to mouse liver chromatin, revealing the counteractive interplay between these two regulators of liver sex-specificity. Our findings establish a close correlation between sex-dependent STAT5 binding and sex-biased target gene expression. Moreover, sex-dependent STAT5 binding correlated positively with sex-biased DNase hypersensitivity and H3-K4me1 and H3-K4me3 (activating) marks, correlated negatively with sex-biased H3-K27me3 (repressive) marks, and was associated with sex-differentially enriched motifs for HNF6/CDP factors. Importantly, BCL6 binding was preferentially associated with repression of female-biased STAT5 targets in male liver. Furthermore, BCL6 and STAT5 common targets but not BCL6 unique targets showed strong enrichment for lipid and drug metabolism. These findings provide a comprehensive, genome-wide view of the mechanisms whereby these two GH-regulated transcription factors establish and maintain sex differences affecting liver physiology and disease. The approaches used here to characterize sex-dependent STAT5 and BCL6 binding can be applied to other condition-specific regulatory factors and binding sites and their interplay with co-operative chromatin-binding factors.
2011-12-18 | GSE31578 | GEO
Project description:We identified genes expressed in mouse liver that are regulated by Cux2, a highly female-specific liver transcription factor whose expression is regulated by sex-dependent plasma GH patterns. Using adenovirus to overexpress Cux2 (Adeno-Cux2) in male liver, we show that Cux2 represses ~35% of male-biased genes and induces/de-represses ~35% of female-biased genes. Adeno-CMV was used as a control for adenoviral infection. (Published in Molec Cell Biology, TL Conforto et al, 2012) Liver RNA isolated from the following eight groups of mice was used in the present study: (1) 8 wk old untreated male (M) mice (n = 10; 5 per each pool); (2) 8 wk old untreated female mice (F) mice (n = 11; 5 or 6 per each pool); (3) 8 wk old male mice treated with Adeno-Cux2 and euthanized 5 days later (n = 12; 6 per each pool); (4) 8 wk old female mice treated with Adeno-Cux2 and euthanized 5 days later (n = 8; 4 per each pool); (5) 8 wk old male mice treated with Adeno-CMV and euthanized 5 days later (n = 13; 6 or 7 per each pool); (6) 8 wk old female mice treated with Adeno-CMV and euthanized 5 days later (n = 7; 3 or 4 per each pool); (7) 8 wk old male mice treated with Adeno-Cux2 and euthanized 3 days later (n=11; 5 or 6 per each pool); (8) 8 wk old male mice treated with Adeno-CMV and euthanized 3 days later (n=11; 5 or 6 per pool). These RNA pools were used in four separate sets of competitive hybridization experiments: 1) 8 wk untreated M vs. 8 wk untreated F; 2) 8 wk M + Ad-Cux2 (5 day) vs. 8 wk M + Ad-CMV (5 day); 3) 8 wk F + Ad-Cux2 (5 day) vs. 8 wk F + Ad-CMV (5 day); 4) 8 wk M + Ad-Cux2 (3 day) vs. 8 wk M + Ad-CMV (3 day). Fluorescent labeling of RNA and hybridization of the Alexa 555-labeled (green) and Alexa 647-labeled (red) RNA samples to Agilent Mouse Gene Expression 4x44k v1 microarrays (Agilent Technology, Palo Alto, CA; catalog # G4122F-014868) were carried out, with dye swapping for each of the three hybridization experiments to eliminate dye bias. Two microarrays, one for each mixed cDNA sample, were hybridized for each of the four fluorescent reverse pairs, giving a total of 8 microarrays.
2012-09-10 | E-GEOD-35897 | biostudies-arrayexpress