期刊
DEVELOPMENT
卷 147, 期 1, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.181966
关键词
5hmC; Id3; Chromatin; Differentiation; Intestinal stem cell
资金
- National Institutes of Health [K01 DK111709, R03 DK122111, R01 DK091427]
- American Gastroenterological Association
- National Institute of Diabetes and Digestive and Kidney Diseases [P30 DK34987]
- Burroughs Wellcome Fund
- U.S. Department of Defense [W81XWH-19-1-0423]
Intestinal stem cell (ISC) plasticity is thought to be regulated by broadly permissive chromatin shared between ISCs and their progeny. Here, we have used a Sox9(EGFP) reporter to examine chromatin across ISC differentiation. We find that open chromatin regions (OCRs) can be defined as broadly permissive or dynamic in a locus-specific manner, with dynamic OCRs found primarily in loci consistent with distal enhancers. By integrating gene expression with chromatin accessibility at transcription factor (TF) motifs in the context of Sox9(EGFP) populations, we classify broadly permissive and dynamic chromatin relative to TF usage. These analyses identify known and potential regulators of ISC differentiation via association with dynamic changes in chromatin. Consistent with computational predictions, Id3-null mice exhibit increased numbers of cells expressing the ISC-specific biomarker OLFM4. Finally, we examine the relationship between gene expression and 5-hydroxymethylcytosine (5hmC) in Sox9(EGFP) populations, which reveals 5hmC enrichment in absorptive lineage-specific genes. Our data demonstrate that intestinal chromatin dynamics can be quantitatively defined in a locus-specific manner, identify novel potential regulators of ISC differentiation and provide a chromatin roadmap for further dissecting cis regulation of cell fate in the intestine.
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