Short-chain fatty acid metabolites propionate and butyrate are unique epigenetic regulatory elements linking diet, metabolism and gene expression

被引：3

作者：

Nshanian, Michael ^{[1
]}

Gruber, Joshua J. ^{[1
]}

Geller, Benjamin S. ^{[1
]}

Chleilat, Faye ^{[1
]}

Lancaster, Samuel M. ^{[1
]}

White, Shannon M. ^{[1
]}

Alexandrova, Ludmila ^{[2
]}

Camarillo, Jeannie M. ^{[3
]}

Kelleher, Neil L. ^{[3
,4
]}

Zhao, Yingming ^{[5
]}

Snyder, Michael P. ^{[1
,6
]}

机构：

[1] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA

[2] Stanford Univ, Vincent Coates Fdn, Mass Spectrometry Lab, Stanford, CA USA

[3] Northwestern Univ, Mol Biosci & Prote Ctr Excellence, Dept Chem, Evanston, IL USA

[4] Northwestern Univ, Feinberg Sch Med, Dept Biochem & Mol Genet, Evanston, IL USA

[5] Univ Chicago, Ben May Dept Canc Res, Chicago, IL USA

[6] Stanford Univ, Sch Med, Ctr Genom & Personalized Med, Stanford, CA 94305 USA

来源：

NATURE METABOLISM | 2025年 / 7卷 / 01期

基金：

美国国家卫生研究院;

关键词：

HISTONE; ACETYLATION; PROPIONYLATION; BUTYRYLATION; CHROMATIN;

D O I：

10.1038/s42255-024-01191-9

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The short-chain fatty acids (SCFAs) propionate and butyrate have beneficial health effects, are produced in large amounts by microbial metabolism and have been identified as unique acyl lysine histone marks. To better understand the function of these modifications, we used chromatin immunoprecipitation followed by sequencing to map the genome-wide location of four short-chain acyl histone marks, H3K18pr, H3K18bu, H4K12pr and H4K12bu, in treated and untreated colorectal cancer (CRC) and normal cells as well as in mouse intestines in vivo. We correlate these marks with open chromatin regions and gene expression to access the function of the target regions. Our data demonstrate that propionate and butyrate bind and act as promoters of genes involved in growth, differentiation and ion transport. We propose a mechanism involving direct modification of specific genomic regions by SCFAs resulting in increased chromatin accessibility and, in the case of butyrate, opposing effects on the proliferation of normal versus CRC cells.

引用

页码：196 / 211

页数：32