Changes in chromatin accessibility in male mouse liver induced by naturally occurring endogenous pulses of plasma growth hormone (GH)-activated STAT5
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ABSTRACT:
PROVIDER: PRJNA545113 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26961653.fastq.gz | Fastqsanger.gz | |||
| SRR26961654.fastq.gz | Fastqsanger.gz | |||
| SRR26961655.fastq.gz | Fastqsanger.gz | |||
| SRR9136440.fastq.gz | Fastqsanger.gz | |||
| SRR9136431.fastq.gz | Fastqsanger.gz |
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Project description:Sequencing files provided here are mouse liver DNase-seq for male mouse livers collected at either a peak or trough of GH/STAT5 activity. This is part of a larger study that includes DNase-seq in mouse liver from hypophysectomized males, females, and hypox-male mice given a single dose of GH. DNase hypersensitivity site (DHS) analysis of these livers established that the naturally occurring, endogenous male rhythm of plasma GH pulse-stimulated liver STAT5 activation induces dynamic, repeated cycles of chromatin opening and closing at several thousand liver DHS and comprises a novel mechanism conferring male bias to liver chromatin accessibility.
2023-08-21 | GSE131848 | GEO
Project description:Sequencing files provided here are mouse liver DNase-seq to identify DNase hypersensitive sites (DHS) in livers from intact and hypox female, hypox male, and hypox male mice given a single injection of GH and then euthanized 30, 90, or 240 minutes later. This is part of a larger study that includes DNase-seq in mouse liver from intact males determined to be STAT5-high or STAT5-low based on an endogenous pulse of GH/STAT5. This allows us to identify GH pulse-responsive DHS and better understand male-biased DHS regulation of sex-biased genes. Overall, our findings establish that pulsatile chromatin opening stimulated by endogenous, physiological hormone pulses is a novel mechanism for establishing widespread sex differences in chromatin accessibility and transcription factor binding, which are closely linked to sex-biased gene expression and the sexual dimorphism of liver function.
2023-08-21 | GSE131852 | 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: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 investigated the effects of a single pulse of growth hormone on the transcriptional activation of STAT5 target genes in hypophysectomized male mouse liver. This GEO series is part of a larger study, where we investigated the impact of a single pulse of GH given to hypophysectomized mice on local liver chromatin accessibility [DNase hypersensitive site analysis], transcription rates [hnRNA analysis], and gene expression [quantitative PCR and RNA-Seq] determined 30, 90 or 240 min later. The STAT5-dependent but sex-independent early GH response genes Igf1 and Cish showed rapid, GH pulse-induced increases in chromatin accessibility and gene transcription, reversing the effects of hypophysectomy. Rapid increases in liver chromatin accessibility and transcriptional activity were also induced in hypophysectomized male mice for some (Ces2b, Ugt2b38) but not for other liver STAT5-dependent male-biased genes (Cyp7b1). Moreover, in pituitary-intact male mice, Igf1, Cish, Ces2b and Ugt2b38 all showed remarkable cycles of chromatin opening and closing, and associated cycles of induced gene transcription, which closely followed each endogenous pulse of liver STAT5 activity. Thus, the endogenous rhythms of male plasma GH pulsation dynamically open and then close liver chromatin at discrete, localized regulatory sites in temporal association with transcriptional activation of Igf1, Cish and a subset of STAT5-dependent male-biased genes.
2017-02-24 | GSE93379 | GEO
Project description:Environmental effects on immunity in naturally-occurring vertebrates
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Project description:The molecular nature of malignant tumors is well studied in vertebrates, while their evolutionary origin remains unknown. In particular, there is no evidence for naturally occurring malignant tumors in pre-bilaterian animals, such as sponges and cnidarians. This is somewhat surprising given that recent computational studies have predicted that all metazoans are prone to develop tumors. Here we provide first evidence for naturally occurring tumors in Hydra oligactis. Histological, cellular and molecular data reveal that these tumors are transplantable and caused by differentiation arrest of female gametes. Growth of tumor cells is independent from the cellular environment. Tumor bearing polyps have significantly reduced fitness. In addition, Hydra tumors show a greatly altered transcriptome that mimics expression shifts in vertebrate cancers. Therefore, this study shows, that invasive tumors have deep roots in animal phylogeny, and that early branching animals may be informative in revealing the fundamental mechanisms of tumorigenesis.
2014-06-24 | GSE56287 | GEO
Project description:We investigated the effects of a single pulse of growth hormone on the transcriptional activation of STAT5 target genes in hypophysectomized male mouse liver. This GEO series is part of a larger study, where we investigated the impact of a single pulse of GH given to hypophysectomized mice on local liver chromatin accessibility [DNase hypersensitive site analysis], transcription rates [hnRNA analysis], and gene expression [quantitative PCR and RNA-Seq] determined 30, 90 or 240 min later. The STAT5-dependent but sex-independent early GH response genes Igf1 and Cish showed rapid, GH pulse-induced increases in chromatin accessibility and gene transcription, reversing the effects of hypophysectomy. Rapid increases in liver chromatin accessibility and transcriptional activity were also induced in hypophysectomized male mice for some (Ces2b, Ugt2b38) but not for other liver STAT5-dependent male-biased genes (Cyp7b1). Moreover, in pituitary-intact male mice, Igf1, Cish, Ces2b and Ugt2b38 all showed remarkable cycles of chromatin opening and closing, and associated cycles of induced gene transcription, which closely followed each endogenous pulse of liver STAT5 activity. Thus, the endogenous rhythms of male plasma GH pulsation dynamically open and then close liver chromatin at discrete, localized regulatory sites in temporal association with transcriptional activation of Igf1, Cish and a subset of STAT5-dependent male-biased genes.
2017-02-24 | GSE93381 | GEO
Project description:Expression profiling of 3T3-F442A adipocytes treated with growth hormone (GH, 500 nM) or vehicle (DMEM + 1% BSA) control for 30 min., 4 hr., or 48 hr in three independent experiments. Chronic GH treatment induces metabolic changes consistent with insulin resistance in 3T3-F442A adipocytes. Keywords: time-course
2005-12-20 | GSE2120 | GEO
Project description:Signal Transducers and Activators of Transcription (STAT) 5A/B regulate cytokine-inducible genes upon binding to GAS motifs. It is not known what percentage of genes with GAS motifs bind to and are regulated by STAT5. Moreover, it is not clear whether genome-wide STAT5 binding is modulated by its concentration. To clarify these issues we established genome-wide STAT5 binding upon growth hormone (GH) stimulation of wild type mouse embryonic fibroblasts (MEFs) and MEFs overexpressing STAT5A more than 20-fold. Upon GH stimulation 23,827 and 111,939 STAT5A binding sites were detected in wild type and STAT5A overexpressing MEFs, respectively. 13,278 and 71,561 peaks contained at least one GAS motif. 1,586 and 8,613 binding sites were located within 2.5 kbp of promoter sequences, respectively. Stringent filtering revealed 78 genes in which the promoter/upstream region (-10kbp to +0.5kbp) was recognized by STAT5 both in wt and STAT5 overexpressing MEFs and 347 genes that bound STAT5 only in overexpressing cells. Genome-wide expression analyses identified that the majority of STAT5-bound genes was not under GH control. Up to 40% of STAT5-bound genes were not expressed. For the first time we demonstrate the magnitude of opportunistic genomic STAT5 binding that does not translate into transcriptional activation of neighboring genes. Genome-wide mapping of STAT5 binding in MEF cells (WT, KO; Stat5-/- and overexpression; STAT5A-Stat5-/-) upon growth hormone induction
2012-01-12 | E-GEOD-34986 | biostudies-arrayexpress