Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape
- J. Gray Camp1,2,3,10,
- Christopher L. Frank4,5,10,
- Colin R. Lickwar5,
- Harendra Guturu6,
- Tomas Rube7,
- Aaron M. Wenger3,
- Jenny Chen8,
- Gill Bejerano2,3,
- Gregory E. Crawford4,9 and
- John F. Rawls1,4,5
- 1Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA;
- 2Department of Developmental Biology, Stanford University, Stanford, California 94305, USA;
- 3Computer Science Department, Stanford University, Stanford, California 94305, USA;
- 4Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina 27708, USA;
- 5Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina 27710, USA;
- 6Department of Electrical Engineering, Stanford University, Stanford, California 94305, USA;
- 7Physics Department, Stanford University, Stanford, California 94305, USA;
- 8Biomedical Informatics Program, Stanford University, Stanford, California 94305, USA;
- 9Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, North Carolina 27708, USA
- Corresponding authors: john.rawls{at}duke.edu, greg.crawford{at}duke.edu
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↵10 These authors contributed equally to this work.
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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.165845.113.
- Received August 29, 2013.
- Accepted June 6, 2014.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
