ArticleBiochimica et biophysica acta2014
GATA4 represses an ileal program of gene expression in the proximal small intestine by inhibiting the acetylation of histone H3, lysine 27.
Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- GATA4 controls regionalization of tissue immunity and commensal-driven immunopathology.Immunity · 2023Article
- Article
- Patterning the gastrointestinal epithelium to confer regional-specific functions.Developmental biology · 2018Review
- Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells.PLoS biology · 2017Article
- Differentiation of Human Pluripotent Stem Cells into Colonic Organoids via Transient Activation of BMP Signaling.Cell stem cell · 2017Article
- GATA4 Is Sufficient to Establish Jejunal Versus Ileal Identity in the Small Intestine.Cellular and molecular gastroenterology and hepatology · 2017Article
- Transcriptional heterogeneity in the lactase gene within cell-type is linked to the epigenome.Scientific reports · 2017Article
- Gata4 is critical to maintain gut barrier function and mucosal integrity following epithelial injury.Scientific reports · 2016Article
- GATA4 regulates epithelial cell proliferation to control intestinal growth and development in mice.Cellular and molecular gastroenterology and hepatology · 2016Article
- Transcription factors GATA4 and HNF4A control distinct aspects of intestinal homeostasis in conjunction with transcription factor CDX2.The Journal of biological chemistry · 2015Article
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
GATA4 is expressed in the proximal 85% of small intestine where it promotes a proximal intestinal ('jejunal') identity while repressing a distal intestinal ('ileal') identity, but its molecular mechanisms are unclear. Here, we tested the hypothesis that GATA4 promotes a jejunal versus ileal identity in mouse intestine by directly activating and repressing specific subsets of absorptive enterocyte genes by modulating the acetylation of histone H3, lysine 27 (H3K27), a mark of active chromatin, at sites of GATA4 occupancy. Global analysis of mouse jejunal epithelium showed a statistically significant association of GATA4 occupancy with GATA4-regulated genes. Occupancy was equally distributed between down- and up-regulated targets, and occupancy sites showed a dichotomy of unique motif over-representation at down- versus up-regulated genes. H3K27ac enrichment at GATA4-binding loci that mapped to down-regulated genes (activation targets) was elevated, changed little upon conditional Gata4 deletion, and was similar to control ileum, whereas H3K27ac enrichment at GATA4-binding loci that mapped to up-regulated genes (repression targets) was depleted, increased upon conditional Gata4 deletion, and approached H3K27ac enrichment in wild-type control ileum. These data support the hypothesis that GATA4 both activates and represses intestinal genes, and show that GATA4 represses an ileal program of gene expression in the proximal small intestine by inhibiting the acetylation of H3K27.
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