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• W2021006437 endingPage "896" @default.
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• W2021006437 abstract "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 versus 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 genome wide, revealing a counteractive interplay between these two regulators of sex differences in liver gene expression. 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 cooperative chromatin binding factors." @default.
• W2021006437 created "2016-06-24" @default.
• W2021006437 creator A5044985980 @default.
• W2021006437 creator A5045362289 @default.
• W2021006437 creator A5062154647 @default.
• W2021006437 date "2012-02-01" @default.
• W2021006437 modified "2023-10-16" @default.
• W2021006437 title "Dynamic, Sex-Differential STAT5 and BCL6 Binding to Sex-Biased, Growth Hormone-Regulated Genes in Adult Mouse Liver" @default.
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• W2021006437 doi "https://doi.org/10.1128/mcb.06312-11" @default.
• W2021006437 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3272977" @default.
• W2021006437 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22158971" @default.
• W2021006437 hasPublicationYear "2012" @default.
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