Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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3'-UTR-seq of female and male mouse pituitary gland across pubertal transition

ABSTRACT: The pituitary gland exhibits sex differences in its function. Diseases associated with dysregulation of the pituitary are also sex-biased in prevalence. Previous qPCR profiling of puberty-related genes in the pituitary gland revealed increasingly sex-biased expression of genes profiled across pubertal transition. Here, we performed 3’-UTR-seq on pituitary gland from both sexes of C57BL/6J mice at 5 ages spanning pubertal transition (postnatal days 12, 22, 27, 32, 37) (6 replicates per sex at each age) to examine genome-wide sex-biased trends in gene expression and potential regulatory mechanisms of these sex differences. QuantSeq 3’mRNA-seq libraries were constructed from total RNA using an automated method with Agilent NGS Workstation. Resulting single-end libraries were sequenced at SickKids TCAG core on the Illumina v4 flow cell with SR50 bp cycles extended to 68 bp. A customized pipeline was developed and used for analysis of reads obtained (see paper for details). Processed reads were mapped to mouse genome (mm10).

INSTRUMENT(S): Illumina HiSeq 2500, Agilent NGS Workstation

ORGANISM(S): Mus musculus

SUBMITTER:

PROVIDER: E-MTAB-9459 | biostudies-arrayexpress |

SECONDARY ACCESSION(S): E-MTAB-9460

REPOSITORIES: biostudies-arrayexpress

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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.

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3'-UTR-seq of female and male mouse pituitary gland across pubertal transition

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