Development of complementary photo-arginine/lysine to promote discovery of Arg/Lys hPTMs interactomes Journal Article


Authors: Zong, Y.; Weiss, N.; Wang, K.; Pagano, A. E.; Heissel, S.; Perveen, S.; Huang, J.
Article Title: Development of complementary photo-arginine/lysine to promote discovery of Arg/Lys hPTMs interactomes
Abstract: Arginine and lysine, frequently appearing as a pair on histones, have been proven to carry diverse modifications and execute various epigenetic regulatory functions. However, the most context-specific and transient effectors of these marks, while significant, have evaded study as detection methods have thus far not reached a standard to capture these ephemeral events. Herein, a pair of complementary photo-arginine/δ-photo-lysine (R-dz/K-dz) probes is developed and involve these into histone peptide, nucleosome, and chromatin substrates to capture and explore the interactomes of Arg and Lys hPTMs. By means of these developed tools, this study identifies that H3R2me2a can recruit MutS protein homolog 6 (MSH6), otherwise repelDouble PHD fingers 2 (DPF2), Retinoblastoma binding protein 4/7 (RBBP4/7). And it is disclosed that H3R2me2a inhibits the chromatin remodeling activity of the cBAF complex by blocking the interaction between DPF2 (one component of cBAF) and the nucleosome. In addition, the novel pairs of H4K5 PTMs and respective readers are highlighted, namely H4K5me-Lethal(3)malignant brain tumor-like protein 2 (L3MBTL2), H4K5me2-L3MBTL2, and H4K5acK8ac-YEATS domain-containing protein 4 (YEATS4). These powerful tools pave the way for future investigation of related epigenetic mechanisms including but not limited to hPTMs. © 2024 The Authors. Advanced Science published by Wiley-VCH GmbH.
Keywords: proteins; metabolism; protein processing; protein processing, post-translational; epigenetics; histone; chromatin; histones; lysine; chromosomes; arginine; nucleosome; nucleosomes; post-translational modification; interactome; post-translational modifications; chromatin remodelling; nucleosome chromatin remodeling; photo-arginine; δ-photo-lysine; malignant brain tumour; regulatory functions
Journal Title: Advanced Science
Volume: 11
Issue: 14
ISSN: 2198-3844
Publisher: Wiley-VCH Verlag GmbH & Co. KGaA  
Date Published: 2024-04-01
Start Page: 2307526
Language: English
DOI: 10.1002/advs.202307526
PUBMED: 38298064
PROVIDER: scopus
PMCID: PMC11005723
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Yu Zong -- Source: Scopus
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MSK Authors
  1. Ke Wang
    6 Wang
  2. Yu Zong
    1 Zong