Format

Send to

Choose Destination
Development. 2020 Jan 3;147(1). pii: dev181966. doi: 10.1242/dev.181966.

Quantitative classification of chromatin dynamics reveals regulators of intestinal stem cell differentiation.

Author information

1
Department of Genetics, University of North Carolina at Chapel Hill, NC 27599, USA.
2
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC 27599, USA.
3
Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, NC 27599, USA.
4
Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, NC 27599, USA.
5
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill/North Carolina State University, NC 27599, USA.
6
Department of Genetics, University of North Carolina at Chapel Hill, NC 27599, USA agracz@med.unc.edu.

Abstract

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 Sox9EGFP 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 Sox9EGFP 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 Sox9EGFP 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.

KEYWORDS:

5hmC; Chromatin; Differentiation; Id3; Intestinal stem cell

PMID:
31862843
PMCID:
PMC6983707
[Available on 2021-01-03]
DOI:
10.1242/dev.181966

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center