Ontology highlight
ABSTRACT:
PROVIDER: PRJNA748855 | ENA |
REPOSITORIES: ENA
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Project description:To determine the potential molecular mechanisms by which STAT5 signaling control ileal Paneth cell homeostasis, we isolated total RNA from ileal intact crypts of STAT5+/+, STAT5DIEC-/- and STAT5DIEC+++ mice and performed RNA sequencing (RNA-seq). With an average of 22.3 million reads per sample, we observed 27540 transcripts when reads were aligned to the mm10 genome with annotations provided by Ensembl. Transcripts were filtered, requiring at least 3 reads in 50% of samples within at least one condition, leaving 10197 transcripts for analysis. To identify differentially-regulated transcripts, we performed ANOVA (FDR-corrected p<0.05) and required the fold change to exceed 1.5.
2019-03-21 | GSE112166 | GEO
Project description:To determine the potential molecular mechanisms by which STAT5 signaling controls colonic crypt homeostasis, we isolated total RNA from ileal intact crypts of STAT5+/+, STAT5DIEC-/- and STAT5DIEC+++ mice and performed RNA sequencing (RNA-seq).
| PRJNA448447 | ENA
Project description:Signal Transducers and Activators of Transcription (STATs) are principal transcription factors downstream of cytokine receptors. Although STAT5A is expressed in most tissues it remains to be understood why its premier, non-redundant functions are restricted to prolactin-induced mammary gland development. We report that the ubiquitously expressed Stat5a/b locus is subject to lineage-specific transcriptional control in mammary epithelium. Genome-wide surveys of epigenetic status and transcription factor occupancy uncovered a putative mammary-specific enhancer within the intergenic sequences separating the two Stat5 genes. This region exhibited several hallmarks of genomic enhancers, including DNaseI hypersensitive sites, H3K27 acetylation and binding by GR and MED1. Mammary-specific STAT5 binding was obtained at two canonical STAT5 binding motifs. CRISPR/Cas9-mediated genome editing was used to delete these STAT5 binding sites in mice and determine their biological function. Mutant animals exhibited an 80% reduction of Stat5 levels in mammary epithelium and a concomitant reduction of STAT5-dependent gene expression. Transcriptome analysis identified a class of mammary-restricted genes that was particularly dependent on high STAT5 levels as a result of the intergenic enhancer. Taken together, the mammary-specific enhancer enables a positive feedback circuit that underlies the remarkable abundance of STAT5 and, in turn, controls the efficacy of STAT5-dependent mammary physiology. ChIP-seq for H3K27ac, RNA Pol II, and MED1 in mammary tissues at L1, and ChIP-seq for H3K27ac and GR in mammary tissues at p13. mRNA-seq in WT at L1, line B (GAS2 mutation only) and line C (both GAS1 and GAS2 mutations) at L1 in mammary tissues, and DNase-seq in WT mammary tissues at L1.
2015-09-05 | E-GEOD-72724 | biostudies-arrayexpress
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:Mammary development is characterized by the proliferation and progressive differentiation of alveolar epithelium during pregnancy, culminating in lactation. These processes are largely controlled by hormones through transcription factors. We now explore the contributions of histone methyltransferases, which establish H3K27me3 marks, in the temporally-regulated differentiation of mammary epithelium. Loss of EZH2, but not EZH1, resulted in precocious mammary differentiation, which was facilitated by STAT5 binding to specific target genes and their activation. Mammary stem cells were not compromised in the absence of EZH2. Genome-wide H3K27me3 patterns remained intact in the absence of EZH2. Mammary-specific loci were devoid of H3K27me3 marks in mammary progenitor and mature cells, suggesting no regulatory role for this repressive mark. Lastly, the combined absence of EZH1 and EZH2 inhibited the formation of alveoli. Taken together, EZH2 controls temporally-restricted differentiation of mammary epithelium through H3K27me3-independent mechanisms. mRNA-seq and ChIP-seq in MMTV-Cre (Control), E1-/- (E1KO), E1+/-;E2f/f;control (E1+/-E2KO) and Ezh2f/f;control (E2KO) mammary gland tissues or MECs (purified mammary epithelial cells). H3K27me3 and STAT5 ChIP-seqs in mammary tissues at p13; H3K4me3 ChIP-seq in MECs (mammary epithelial cells) at p13; RNA-seqs at mature virgin (with/without prolactin injection), p13 and p18 mammary tissues.
2013-12-31 | E-GEOD-52016 | biostudies-arrayexpress
Project description:To investigate the role of RAD21 in the transcriptional regulation of global gene expression at early stage of colorectal cancer developments, we peformed the genome-wide analysis to map genomic regions bound by Rad21 in normal small testinal crypts and tumors (adenomas) harvested from Apc Min/+ mice using ChIP-seq. ChIP-seq naalysis identified high confidence RAD21 binding sites unique to normal crypts or adenomas, as well as those common to both tissues. We further performed RNA-seq to profile the changes in gene expression from normal WT crypts to adenomas at the very early stage of adenomagenesis in the context of Rad21 heterozygous loss. mRNA profiles of normal small intestinal crypts (WT) and adenomas from Apc Min/+ and Apc Min/+:Rad21+/- double mutant mouse; Mapping of Rad21 genomic binding sites in normal intestinal crypts (WT) and Apc Min/+ adenomas
2014-10-31 | E-GEOD-59283 | biostudies-arrayexpress
Project description:Super-enhancers comprise of dense transcription factor platforms highly enriched for active chromatin marks. A paucity of functional data led us to investigate their role in the mammary gland, an organ characterized by exceptional gene regulatory dynamics during pregnancy. ChIP-Seq for the master regulator STAT5, the glucocorticoid receptor, H3K27ac and MED1, identified 440 mammary-specific super-enhancers, half of which were associated with genes activated during pregnancy. We interrogated the Wap super-enhancer, generating mice carrying mutations in STAT5 binding sites within its three constituent enhancers. Individually, only the most distal site displayed significant enhancer activity. However, combinatorial mutations showed that the 1,000-fold gene induction relied on all enhancers. Disabling the binding sites of STAT5, NFIB and ELF5 in the proximal enhancer incapacitated the entire super-enhancer, suggesting an enhancer hierarchy. The identification of mammary-specific super-enhancers and the mechanistic exploration of the Wap locus provide insight into the complexity of cell-specific and hormone-regulated genes. ChIP-Seq for STAT5A, GR, H3K27ac, MED1, NFIB, ELF5, RNA Pol II, and H3K4me3 in wild type (WT) mammary tissues at day one of lactation (L1), and ChIP-Seq for STAT5A, GR, H3K27ac, MED1, NFIB, ELF5, and H3K4me3 in WT mammary tissues at day 13 of pregnancy (p13). ChIP-Seq for STAT5A, GR, H3K27a in Wap-delE1a, -delE1b, -delE1c, -delE2 and -delE3 mutant mammary tissues at L1, and ChIP-Seq for NFIB and ELF5 in Wap-delE1b and -delE1c mutant mammary tissues at L1. ChIP-Seq for H3K4me3 in mammary-epthelial cells at p13 and L1. DNase-seq in WT mammary tissues at L1 and DNase-seq in Wap-delE1a, -delE1c, and -delE3 mutant mammary tissues at L1.
2016-05-31 | E-GEOD-74826 | biostudies-arrayexpress
Project description:DNase-seq and ChIP-seq determine that C/EBP maintains chromatin accessibility in liver and facilitates glucocorticoid receptor recruitment to steroid response elements DNase-seq and ChIP-seq (GR, C/EBPb and RNAPII) in intact liver from adrenalectomized mice injected with dex (1h)
2013-04-17 | E-GEOD-46047 | biostudies-arrayexpress
Project description:To assess the role of LSD1 in mouse small intestinal epithelium, we isolated small intestinal crypts from wild type (WT) (Villin-Cre -; Lsd1f/f) and intestinal-epithelial-specific knock-out (KO) (Villin-Cre+; Lsd1f/f) mice. We dissociated crypts into single cells, and FACS sorted Epcam+ cells, to avoid immune-cell contamination. RNA was directly isolated from these sorted cells, and this was used for RNA seq. As KO crypts are different from WT crypts (KO crypts lack Paneth cells), identifying genes specifically regulated by LSD1 helps us to identify how LSD1 regulates intestinal crypt biology. Specifically, because we were able to combine this with ChIP-seq of the same cells, to identify where H3K4me1 levels (target of the histone demethylase LSD1) were different in the genome.
2020-11-16 | E-MTAB-7862 | biostudies-arrayexpress
Project description:RNA-seq analysis of intact male and female adult 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 | GSE93380 | GEO