The microbiota programs DNA methylation to control intestinal homeostasis and inflammation.
Animals
Colitis
/ chemically induced
Colon
/ metabolism
DNA
/ genetics
DNA Methylation
Dextran Sulfate
/ administration & dosage
Epigenesis, Genetic
Gastrointestinal Microbiome
/ physiology
Genome
Germ-Free Life
Homeostasis
/ genetics
Inflammation
Male
Mice
Mice, Inbred C57BL
Symbiosis
/ genetics
Whole Genome Sequencing
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
21
01
2019
accepted:
11
12
2019
pubmed:
6
2
2020
medline:
17
7
2020
entrez:
5
2
2020
Statut:
ppublish
Résumé
Although much research has been done on the diversity of the gut microbiome, little is known about how it influences intestinal homeostasis under normal and pathogenic conditions. Epigenetic mechanisms have recently been suggested to operate at the interface between the microbiota and the intestinal epithelium. We performed whole-genome bisulfite sequencing on conventionally raised and germ-free mice, and discovered that exposure to commensal microbiota induced localized DNA methylation changes at regulatory elements, which are TET2/3-dependent. This culminated in the activation of a set of 'early sentinel' response genes to maintain intestinal homeostasis. Furthermore, we demonstrated that exposure to the microbiota in dextran sodium sulfate-induced acute inflammation results in profound DNA methylation and chromatin accessibility changes at regulatory elements, leading to alterations in gene expression programs enriched in colitis- and colon-cancer-associated functions. Finally, by employing genetic interventions, we show that microbiota-induced epigenetic programming is necessary for proper intestinal homeostasis in vivo.
Identifiants
pubmed: 32015497
doi: 10.1038/s41564-019-0659-3
pii: 10.1038/s41564-019-0659-3
doi:
Substances chimiques
DNA
9007-49-2
Dextran Sulfate
9042-14-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
610-619Commentaires et corrections
Type : CommentIn
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