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Genome Res. 2014 Sep;24(9):1504-16. doi: 10.1101/gr.165845.113. Epub 2014 Jun 24.

Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape.

Author information

1
Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; Department of Developmental Biology, Stanford University, Stanford, California 94305, USA; Computer Science Department, Stanford University, Stanford, California 94305, USA;
2
Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina 27708, USA; Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina 27710, USA;
3
Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina 27710, USA;
4
Department of Electrical Engineering, Stanford University, Stanford, California 94305, USA;
5
Physics Department, Stanford University, Stanford, California 94305, USA;
6
Computer Science Department, Stanford University, Stanford, California 94305, USA;
7
Biomedical Informatics Program, Stanford University, Stanford, California 94305, USA;
8
Department of Developmental Biology, Stanford University, Stanford, California 94305, USA; Computer Science Department, Stanford University, Stanford, California 94305, USA;
9
Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina 27708, USA; Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, North Carolina 27708, USA.
10
Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina 27708, USA; Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina 27710, USA; john.rawls@duke.edu greg.crawford@duke.edu.

Abstract

Microbiota regulate intestinal physiology by modifying host gene expression along the length of the intestine, but the underlying regulatory mechanisms remain unresolved. Transcriptional specificity occurs through interactions between transcription factors (TFs) and cis-regulatory regions (CRRs) characterized by nucleosome-depleted accessible chromatin. We profiled transcriptome and accessible chromatin landscapes in intestinal epithelial cells (IECs) from mice reared in the presence or absence of microbiota. We show that regional differences in gene transcription along the intestinal tract were accompanied by major alterations in chromatin accessibility. Surprisingly, we discovered that microbiota modify host gene transcription in IECs without significantly impacting the accessible chromatin landscape. Instead, microbiota regulation of host gene transcription might be achieved by differential expression of specific TFs and enrichment of their binding sites in nucleosome-depleted CRRs near target genes. Our results suggest that the chromatin landscape in IECs is preprogrammed by the host in a region-specific manner to permit responses to microbiota through binding of open CRRs by specific TFs.

PMID:
24963153
PMCID:
PMC4158762
DOI:
10.1101/gr.165845.113
[Indexed for MEDLINE]
Free PMC Article
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