Biological Sciences Division
Published January 19, 2022 | Version v1
Journal article Open

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

Creators

  • 1. University of Copenhagen
  • 2. University of Chicago
  • 3. East China Normal University

Description

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-N-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.

Data availability

All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.

Files

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Additional details

Identifiers

DOI
10.1126/sciadv.abi6696
Other
oai:uchicago.tind.io:11018

Funding

National Institutes of Health
GM135504
National Institutes of Health
DK118266
National Institutes of Health
CA251677
National Institutes of Health
AR078555
European Research Council
ERC-CoG-725172–SIRFUNCT
Carlsbergfondet
2013-01-0333
Carlsbergfondet
CF15-011
danish independent research council
6108-00166B
Danish Independent Research Fund-Technical and Production Sciences
0136-00412B
Ministry of Science and Technology of China
2017YFA054201

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Ben May Department for Cancer Research