title: Identification of 'erasers' for lysine crotonylated histone marks using a chemical proteomics approach.
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.
authors.affiliation: Department of Chemistry, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Xiucong
authors.initials: X
authors.lastname: Bao
authors.affiliation: Department of Physiology, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Chemistry, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Chemistry, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Xiao-Meng
authors.initials: XM
authors.lastname: Li
authors.affiliation: Department of Chemistry, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Chemistry, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Tangpo
authors.initials: T
authors.lastname: Yang
authors.affiliation: School of Biological Sciences, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Chi Fat
authors.initials: CF
authors.lastname: Wong
authors.affiliation: School of Biological Sciences, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Jiangwen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Physiology, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Quan
authors.initials: Q
authors.lastname: Hao
authors.affiliation: Department of Chemistry, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Xiang David
authors.initials: XD
authors.lastname: Li
mesh_terms: D001710:Biotin / Q000737:chemistry; D057930:Click Chemistry; D003437:Crotonates / Q000737:chemistry / Q000378:metabolism*; D015894:Genome, Human; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007553:Isotope Labeling; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056565:Sirtuin 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056566:Sirtuin 3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019809:Streptavidin / Q000737:chemistry
chemical_list: D003437:Crotonates; D006657:Histones; D010455:Peptides; D011994:Recombinant Proteins; D001710:Biotin; D019809:Streptavidin; C447939:SIRT1 protein, human; C474199:SIRT2 protein, human; C466093:SIRT3 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2; D056566:Sirtuin 3; D008239:Lysine
keywords: E. coli; biochemistry; chemical proteomics; crotonylation; posttranslational modification