biostudies-literatureUnknown298(8)Kikuchi MAcetylated lysine residues (Kac) in histones are recognized by epigenetic reader proteins, such as Yaf9, ENL, AF9, Taf14, and Sas5 (YEATS) domain-containing proteins. Human YEATS domains bind to the acetylated N-terminal tail of histone H3; however, their Kac-binding preferences at the level of the nucleosome are unknown. Through genetic code reprogramming, here, we established a nucleosome core particle (NCP) array containing histones that were acetylated at specific residues and used it to compare the Kac-binding preferences of human YEATS domains. We found that AF9-YEATS showed basal binding to the unmodified NCP and that it bound stronger to the NCP containing a single acetylation at one of K4, K9, K14, or K27 of H3, or to histone H4 multi-acetylated between K5 and K16. Crystal structuThe Journal of biological chemistry102164https://www.ebi.ac.uk/biostudies/studies/S-EPMC9293779biostudies-literatureElucidation of binding preferences of YEATS domains to site-specific acetylated nucleosome core particles.PMC9293779Kikuchi MWakamori MGoto MUmehara TMorita SKatsura KShirouzu MHanada KfalseElucidation of binding preferences of YEATS domains to site-specific acetylated nucleosome core particles.Acetylated lysine residues (Kac) in histones are recognized by epigenetic reader proteins, such as Yaf9, ENL, AF9, Taf14, and Sas5 (YEATS) domain-containing proteins. Human YEATS domains bind to the acetylated N-terminal tail of histone H3; however, their Kac-binding preferences at the level of the nucleosome are unknown. Through genetic code reprogramming, here, we established a nucleosome core particle (NCP) array containing histones that were acetylated at specific residues and used it to compare the Kac-binding preferences of human YEATS domains. We found that AF9-YEATS showed basal binding to the unmodified NCP and that it bound stronger to the NCP containing a single acetylation at one of K4, K9, K14, or K27 of H3, or to histone H4 multi-acetylated between K5 and K16. Crystal structu2022-01-01T00:00:00Z2022 Aug2026-05-09T23:42:51.591Z2025-04-04T22:12:11.131ZS-EPMC92937793573220910.1016/j.jbc.2022.102164