title: Crosstalk of homocysteinylation, methylation and acetylation on histone H3.
abstract: Homocysteine (hcy) is an intermediate metabolite in the metabolic pathway of cysteine and methionine. As a non-coded amino acid, hcy is not normally incorporated into protein. However, homocysteine can be recognized and activated by methionyl-tRNA synthetase (MetRs) to produce Hcy-thiolactone (HTL), which can react with the ε-amino group of a protein lysine residue. The N-hcy-linked protein carrying a free thiol group can influence protein structure and function, thus leading to severe diseases. Histone has multiple specific dynamic post-translational modifications (PTMs), especially on the N-terminal tail of histones enriched with lysine and arginine residues. In this study, we confirmed that histone H3 can be modified by HTL on lysine residue. Relative and absolute quantification methods based on mass spectrometry demonstrated the crosstalk between methylation and acetylation of H3 in response to excess HTL. Overall, our data provide novel insights into histone modifications and the regulatory mechanisms of diseases related to homocysteinylation.
authors: Minhang Hospital and Institutes of Biomedical Sciences, Fudan University Shanghai Medical College, 131 Dongan Road, Shanghai 200032, China. hongxiuyu@fudan.edu.cn pyyang@fudan.edu.cn.
authors: Leilei
authors: L
authors: Xu
authors: Jiajia
authors: J
authors: Chen
authors: Jun
authors: J
authors: Gao
authors: Hongxiu
authors: H
authors: Yu
authors: Pengyuan
authors: P
authors: Yang
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D045325:HCT116 Cells; D057809:HEK293 Cells; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways; D008745:Methylation; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational
chemical_list: D006657:Histones; D006710:Homocysteine; C007957:homocysteine thiolactone