Nucleosome conformation dictates the histone code

• DOI: 10.7554/elife.78866
• Publication Date: 2024-02-06T14:15:06Z
• Authors: Matthew R Marunde; Harrison A Fuchs; Jonathan M Burg; Irina K Popova; Anup Vaidya; Nathan W Hall; Ellen N Weinzapfel; Matthew J Meiners; Rachel Watson; Zachary B Gillespie; Hailey F Taylor; Laylo Mukhsinova; Ugochi C Onuoha; Sarah A Howard; Katherine Novitzky; Eileen T McAnarney; Krzysztof Krajewski; Martis W Cowles; Marcus A Cheek; Zu-Wen Sun; Bryan J Venters; Michael-C Keogh; Catherine A Musse...
• Keywords: Histone code; Histone Methylation; PHD finger; Epigenomics; H3K4me3

Histone post-translational modifications (PTMs) play a critical role in chromatin regulation. It has been proposed that these PTMs form localized 'codes' are read by specialized regions (reader domains) chromatin-associated proteins (CAPs) to regulate downstream function. Substantial effort made define [CAP: histone PTM] specificities, and thus decipher the code guide epigenetic therapies. However, this largely done using reductive approach of isolated reader domains peptides, which cannot account for any higher-order factors. Here, we show [BPTF PHD finger bromodomain: interaction is dependent on nucleosome context. The tandem selectively associates with nucleosomal H3K4me3 H3K14ac or H3K18ac, combinatorial engagement despite being cis not predicted peptides. This vitro specificity BPTF PTM-defined nucleosomes recapitulated cellular We propose regulatable tail accessibility its impact binding potential necessitates refine 'histone code' concept interrogate it at level.