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Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases.

Abstract：

:The recently discovered histone post-translational modification crotonylation connects cellular metabolism to gene regulation. Its regulation and tissue-specific functions are poorly understood. We characterize histone crotonylation in intestinal epithelia and find that histone H3 crotonylation at lysine 18 is a surprisingly abundant modification in the small intestine crypt and colon, and is linked to gene regulation. We show that this modification is highly dynamic and regulated during the cell cycle. We identify class I histone deacetylases, HDAC1, HDAC2, and HDAC3, as major executors of histone decrotonylation. We show that known HDAC inhibitors, including the gut microbiota-derived butyrate, affect histone decrotonylation. Consistent with this, we find that depletion of the gut microbiota leads to a global change in histone crotonylation in the colon. Our results suggest that histone crotonylation connects chromatin to the gut microbiota, at least in part, via short-chain fatty acids and HDACs.

journal_name

Nat Commun

journal_title

Nature communications

authors

Fellows R,Denizot J,Stellato C,Cuomo A,Jain P,Stoyanova E,Balázsi S,Hajnády Z,Liebert A,Kazakevych J,Blackburn H,Corrêa RO,Fachi JL,Sato FT,Ribeiro WR,Ferreira CM,Perée H,Spagnuolo M,Mattiuz R,Matolcsi C,Guedes J

doi

10.1038/s41467-017-02651-5

subject

Has Abstract

pub_date

2018-01-09 00:00:00

pages

105

issue

1

issn

2041-1723

pii

10.1038/s41467-017-02651-5

journal_volume

9

pub_type

杂志文章

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