title: Histone Acetylation near the Nucleosome Dyad Axis Enhances Nucleosome Disassembly by RSC and SWI/SNF.
abstract: Signaling associated with transcription activation occurs through posttranslational modification of histones and is best exemplified by lysine acetylation. Lysines are acetylated in histone tails and the core domain/lateral surface of histone octamers. While acetylated lysines in histone tails are frequently recognized by other factors referred to as "readers," which promote transcription, the mechanistic role of the modifications in the lateral surface of the histone octamer remains unclear. By using X-ray crystallography, we found that acetylated lysines 115 and 122 in histone H3 are solvent accessible, but in biochemical assays they appear not to interact with the bromodomains of SWI/SNF and RSC to enhance recruitment or nucleosome mobilization, as previously shown for acetylated lysines in H3 histone tails. Instead, we found that acetylation of lysines 115 and 122 increases the predisposition of nucleosomes for disassembly by SWI/SNF and RSC up to 7-fold, independent of bromodomains, and only in conjunction with contiguous nucleosomes. Thus, in combination with SWI/SNF and RSC, acetylation of lateral surface lysines in the histone octamer serves as a crucial regulator of nucleosomal dynamics distinct from the histone code readers and writers.
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, UT M. D. Anderson Cancer Center, Smithville, Texas, USA.
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Chatterjee
authors.affiliation: Department of Physics, Ohio State University, Columbus, Ohio, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: North
authors.affiliation: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado, USA Howard Hughes Medical Institute, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Mekonnen Lemma
authors.initials: ML
authors.lastname: Dechassa
authors.affiliation: Department of Chemistry and Biochemistry, Ohio State University, Columbus, Ohio, USA.
authors.forename: Mridula
authors.initials: M
authors.lastname: Manohar
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, UT M. D. Anderson Cancer Center, Smithville, Texas, USA.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Prasad
authors.affiliation: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado, USA Howard Hughes Medical Institute, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Karolin
authors.initials: K
authors.lastname: Luger
authors.affiliation: Department of Chemistry and Biochemistry, Ohio State University, Columbus, Ohio, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Ottesen
authors.affiliation: Department of Physics, Ohio State University, Columbus, Ohio, USA Department of Chemistry and Biochemistry, Ohio State University, Columbus, Ohio, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Poirier
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, UT M. D. Anderson Cancer Center, Smithville, Texas, USA bbartholomew@mdanderson.org.
authors.forename: Blaine
authors.initials: B
authors.lastname: Bartholomew
mesh_terms: D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000032:analysis / Q000378:metabolism; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014981:Xenopus
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; C103337:RSC complex, S cerevisiae; C072981:SWI3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; D008239:Lysine