title: Impact of the gut microbiota on enhancer accessibility in gut intraepithelial lymphocytes.
abstract: The gut microbiota impacts many aspects of host biology including immune function. One hypothesis is that microbial communities induce epigenetic changes with accompanying alterations in chromatin accessibility, providing a mechanism that allows a community to have sustained host effects even in the face of its structural or functional variation. We used Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) to define chromatin accessibility in predicted enhancer regions of intestinal αβ+and γδ+intraepithelial lymphocytes purified from germ-free mice, their conventionally raised (CONV-R) counterparts, and mice reared germ free and then colonized with CONV-R gut microbiota at the end of the suckling-weaning transition. Characterizing genes adjacent to traditional enhancers and super-enhancers revealed signaling networks, metabolic pathways, and enhancer-associated transcription factors affected by the microbiota. Our results support the notion that epigenetic modifications help define microbial community-affiliated functional features of host immune cell lineages.
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Semenkovich
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Planer
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Philip P
authors.initials: PP
authors.lastname: Ahern
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Griffin
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030.
authors.forename: Charles Y
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110; jgordon@wustl.edu.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Gordon
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D019070:Cell Lineage; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D000069196:Gastrointestinal Microbiome; D005856:Germ-Free Life; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D000075942:Intraepithelial Lymphocytes / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction
chemical_list: D002843:Chromatin
keywords: ATAC-seq; enhancers of gut intraepithelial lymphocytes; gnotobiotic mice; gut microbiota–immune cell interactions; transcription factors