Short-chain fatty acids activate acetyltransferase p300

Short-chain fatty acids (SCFAs) acetate, propionate, and butyrate are produced in large quantities by the gut microbiome and contribute to a wide array of physiological processes. While the underlying mechanisms are largely unknown, many effects of SCFAs have been traced to changes in the cell’s epi...

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Autores principales:	Sydney P Thomas, John M Denu
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	p300/CBP short-chain fatty acids acyl-coenzyme a acyl-coa acyltransferase epigenetics fatty acid metabolism Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/68c29386651a45138a31431ae35077c1
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spelling	oai:doaj.org-article:68c29386651a45138a31431ae35077c12021-11-11T15:14:53ZShort-chain fatty acids activate acetyltransferase p30010.7554/eLife.721712050-084Xe72171https://doaj.org/article/68c29386651a45138a31431ae35077c12021-10-01T00:00:00Zhttps://elifesciences.org/articles/72171https://doaj.org/toc/2050-084XShort-chain fatty acids (SCFAs) acetate, propionate, and butyrate are produced in large quantities by the gut microbiome and contribute to a wide array of physiological processes. While the underlying mechanisms are largely unknown, many effects of SCFAs have been traced to changes in the cell’s epigenetic state. Here, we systematically investigate how SCFAs alter the epigenome. Using quantitative proteomics of histone modification states, we identified rapid and sustained increases in histone acetylation after the addition of butyrate or propionate, but not acetate. While decades of prior observations would suggest that hyperacetylation induced by SCFAs are due to inhibition of histone deacetylases (HDACs), we found that propionate and butyrate instead activate the acetyltransferase p300. Propionate and butyrate are rapidly converted to the corresponding acyl-CoAs which are then used by p300 to catalyze auto-acylation of the autoinhibitory loop, activating the enzyme for histone/protein acetylation. This data challenges the long-held belief that SCFAs mainly regulate chromatin by inhibiting HDACs, and instead reveals a previously unknown mechanism of HAT activation that can explain how an influx of low levels of SCFAs alters global chromatin states.Sydney P ThomasJohn M DenueLife Sciences Publications Ltdarticlep300/CBPshort-chain fatty acidsacyl-coenzyme a acyl-coa acyltransferaseepigeneticsfatty acid metabolismMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	p300/CBP short-chain fatty acids acyl-coenzyme a acyl-coa acyltransferase epigenetics fatty acid metabolism Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	p300/CBP short-chain fatty acids acyl-coenzyme a acyl-coa acyltransferase epigenetics fatty acid metabolism Medicine R Science Q Biology (General) QH301-705.5 Sydney P Thomas John M Denu Short-chain fatty acids activate acetyltransferase p300
description	Short-chain fatty acids (SCFAs) acetate, propionate, and butyrate are produced in large quantities by the gut microbiome and contribute to a wide array of physiological processes. While the underlying mechanisms are largely unknown, many effects of SCFAs have been traced to changes in the cell’s epigenetic state. Here, we systematically investigate how SCFAs alter the epigenome. Using quantitative proteomics of histone modification states, we identified rapid and sustained increases in histone acetylation after the addition of butyrate or propionate, but not acetate. While decades of prior observations would suggest that hyperacetylation induced by SCFAs are due to inhibition of histone deacetylases (HDACs), we found that propionate and butyrate instead activate the acetyltransferase p300. Propionate and butyrate are rapidly converted to the corresponding acyl-CoAs which are then used by p300 to catalyze auto-acylation of the autoinhibitory loop, activating the enzyme for histone/protein acetylation. This data challenges the long-held belief that SCFAs mainly regulate chromatin by inhibiting HDACs, and instead reveals a previously unknown mechanism of HAT activation that can explain how an influx of low levels of SCFAs alters global chromatin states.
format	article
author	Sydney P Thomas John M Denu
author_facet	Sydney P Thomas John M Denu
author_sort	Sydney P Thomas
title	Short-chain fatty acids activate acetyltransferase p300
title_short	Short-chain fatty acids activate acetyltransferase p300
title_full	Short-chain fatty acids activate acetyltransferase p300
title_fullStr	Short-chain fatty acids activate acetyltransferase p300
title_full_unstemmed	Short-chain fatty acids activate acetyltransferase p300
title_sort	short-chain fatty acids activate acetyltransferase p300
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/68c29386651a45138a31431ae35077c1
work_keys_str_mv	AT sydneypthomas shortchainfattyacidsactivateacetyltransferasep300 AT johnmdenu shortchainfattyacidsactivateacetyltransferasep300
_version_	1718436090071744512

Short-chain fatty acids activate acetyltransferase p300

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