Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape
Year: 2014
Type: preprint
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.
Source: Genome Research
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funders: National Science Foundation, Pharmaceutical Research and Manufacturers of America Foundation, National Institutes of Health, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Characterization of regulatory elements leading to human limb malformations, Microbial regulation of host nutrient metabolism, G1725009932, G3122842006, G402423035, G4652807757, G5226019929, Graduate Research Fellowship Program, Identifying Microbial, Epithelial and Immune Cell Interactions that Mediate Mucosal Homeostasis and Determine IBD Phenotypes, G8629012171, G9000019418, G9000062106, G9000075921, National Gnotobiotic Resource Center, Training in Bioinformatics and Integrative Genomics, Cancer Center Support Grant (CCSG)
OpenAlex ID: W4297933854