Impact of the gut microbiota on enhancer accessibility in gut intraepithelial lymphocytes. Proc Natl Acad Sci U S A 2016 Dec 20;113(51):14805-14810
Date
12/03/2016Pubmed ID
27911843Pubmed Central ID
PMC5187723DOI
10.1073/pnas.1617793113Scopus ID
2-s2.0-85006930186 (requires institutional sign-in at Scopus site) 31 CitationsAbstract
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.
Author List
Semenkovich NP, Planer JD, Ahern PP, Griffin NW, Lin CY, Gordon JIAuthor
Nicholas Semenkovich MD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cell Lineage
Chromatin
Enhancer Elements, Genetic
Gastrointestinal Microbiome
Germ-Free Life
Intestinal Mucosa
Intestines
Intraepithelial Lymphocytes
Male
Mice
Mice, Inbred C57BL
Signal Transduction
