title: Multivalent di-nucleosome recognition enables the Rpd3S histone deacetylase complex to tolerate decreased H3K36 methylation levels.
abstract: The Rpd3S histone deacetylase complex represses cryptic transcription initiation within coding regions by maintaining the hypo-acetylated state of transcribed chromatin. Rpd3S recognizes methylation of histone H3 at lysine 36 (H3K36me), which is required for its deacetylation activity. Rpd3S is able to function over a wide range of H3K36me levels, making this a unique system to examine how chromatin regulators tolerate the reduction of their recognition signal. Here, we demonstrated that Rpd3S makes histone modification-independent contacts with nucleosomes, and that Rpd3S prefers di-nucleosome templates since two binding surfaces can be readily accessed simultaneously. Importantly, this multivalent mode of interaction across two linked nucleosomes allows Rpd3S to tolerate a two-fold intramolecular reduction of H3K36me. Our data suggest that chromatin regulators utilize an intrinsic di-nucleosome-recognition mechanism to prevent compromised function when their primary recognition modifications are diluted.
authors.affiliation: Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX 75390-9148, USA.
authors.forename: Jae-Wan
authors.initials: JW
authors.lastname: Huh
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Chul-Hwan
authors.initials: CH
authors.lastname: Lee
authors.forename: Miyong
authors.initials: M
authors.lastname: Yun
authors.forename: Daniel
authors.initials: D
authors.lastname: Gilada
authors.forename: Chad A
authors.initials: CA
authors.lastname: Brautigam
authors.forename: Bing
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008745:Methylation; D009707:Nucleosomes / Q000378:metabolism*; D014981:Xenopus
chemical_list: D006657:Histones; D009707:Nucleosomes; D006655:Histone Deacetylases