期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 51, 页码 14805-14810出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1617793113
关键词
gut microbiota-immune cell interactions; ATAC-seq; enhancers of gut intraepithelial lymphocytes; transcription factors; gnotobiotic mice
资金
- NIH [DK30292, DK70977, DK078669, T32HG000045, GM007200]
- Sir Henry Wellcome Postdoctoral Fellowship [096100]
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 alpha beta(+) and gamma delta(+) 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.
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