SRA

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 ATAC-seq to define chromatin accessibility in predicted enhancer regions of intestinal aß+ and ?d+ intraepithelial lymphocytes (IELs) purified from germ-free mice, their conventionally-raised (CONV-R) counterparts, and mice reared GF and then colonized with a 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. Overall design: We interrogated chromatin accessibility using ATAC-seq in four cell types derived from mice (CD4+ T cells, CD8+ T cells, aß+ intraepithelial lymphocytes, and ?d+ intraepithelial lymphocytes), across three gut microbial colonization states (germ-free, conventionally-raised, and conventionalized).