Identification of ‘erasers’ for lysine crotonylated histone marks using a chemical proteomics approach

Author:

Bao Xiucong1,Wang Yi2,Li Xin1,Li Xiao-Meng1,Liu Zheng1,Yang Tangpo1,Wong Chi Fat3,Zhang Jiangwen3,Hao Quan2,Li Xiang David1

Affiliation:

1. Department of Chemistry, University of Hong Kong, Hong Kong, Hong Kong

2. Department of Physiology, University of Hong Kong, Hong Kong, Hong Kong

3. School of Biological Sciences, University of Hong Kong, Hong Kong, Hong Kong

Abstract

Posttranslational modifications (PTMs) play a crucial role in a wide range of biological processes. Lysine crotonylation (Kcr) is a newly discovered histone PTM that is enriched at active gene promoters and potential enhancers in mammalian cell genomes. However, the cellular enzymes that regulate the addition and removal of Kcr are unknown, which has hindered further investigation of its cellular functions. Here we used a chemical proteomics approach to comprehensively profile ‘eraser’ enzymes that recognize a lysine-4 crotonylated histone H3 (H3K4Cr) mark. We found that Sirt1, Sirt2, and Sirt3 can catalyze the hydrolysis of lysine crotonylated histone peptides and proteins. More importantly, Sirt3 functions as a decrotonylase to regulate histone Kcr dynamics and gene transcription in living cells. This discovery not only opens opportunities for examining the physiological significance of histone Kcr, but also helps to unravel the unknown cellular mechanisms controlled by Sirt3, that have previously been considered solely as a deacetylase.

Funder

Research Grants Council, University Grants Committee, Hong Kong

University of Hong Kong

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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