Class I histone deacetylases (HDAC1-3) are histone lysine delactylases

Lysine L-lactylation [K(L-la)] is a newly discovered histone mark stimulated under conditions of high glycolysis, such as the Warburg effect. K(L-la) is associated with functions that are different from the widely studied histone acetylation. While K(L-la) can be introduced by the acetyltransferase...

Full description

Saved in:

Bibliographic Details
Published in:	Science advances 2022-01, Vol.8 (3), p.eabi6696-eabi6696
Main Authors:	Moreno-Yruela, Carlos, Zhang, Di, Wei, Wei, Bæk, Michael, Liu, Wenchao, Gao, Jinjun, Danková, Daniela, Nielsen, Alexander L, Bolding, Julie E, Yang, Lu, Jameson, Samuel T, Wong, Jiemin, Olsen, Christian A, Zhao, Yingming
Format:	Article
Language:	eng
Subjects:	Acetylation Biochemistry Biomedicine and Life Sciences Histone Deacetylases - metabolism Histones - metabolism Lysine - metabolism Molecular Biology SciAdv r-articles
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Lysine L-lactylation [K(L-la)] is a newly discovered histone mark stimulated under conditions of high glycolysis, such as the Warburg effect. K(L-la) is associated with functions that are different from the widely studied histone acetylation. While K(L-la) can be introduced by the acetyltransferase p300, histone delactylases enzymes remained unknown. Here, we report the systematic evaluation of zinc- and nicotinamide adenine dinucleotide–dependent histone deacetylases (HDACs) for their ability to cleave ε- -L-lactyllysine marks. Our screens identified HDAC1–3 and SIRT1–3 as delactylases in vitro. HDAC1–3 show robust activity toward not only K(L-la) but also K(D-la) and diverse short-chain acyl modifications. We further confirmed the de-L-lactylase activity of HDACs 1 and 3 in cells. Together, these data suggest that histone lactylation is installed and removed by regulatory enzymes as opposed to spontaneous chemical reactivity. Our results therefore represent an important step toward full characterization of this pathway’s regulatory elements.
ISSN:	2375-2548 2375-2548