title: Conserved molecular interactions within the HBO1 acetyltransferase complexes regulate cell proliferation.
abstract: Acetyltransferase complexes of the MYST family with distinct substrate specificities and functions maintain a conserved association with different ING tumor suppressor proteins. ING complexes containing the HBO1 acetylase are a major source of histone H3 and H4 acetylation in vivo and play critical roles in gene regulation and DNA replication. Here, our molecular dissection of HBO1/ING complexes unravels the protein domains required for their assembly and function. Multiple PHD finger domains present in different subunits bind the histone H3 N-terminal tail with a distinct specificity toward lysine 4 methylation status. We show that natively regulated association of the ING4/5 PHD domain with HBO1-JADE determines the growth inhibitory function of the complex, linked to its tumor suppressor activity. Functional genomic analyses indicate that the p53 pathway is a main target of the complex, at least in part through direct transcription regulation at the initiation site of p21/CDKN1A. These results demonstrate the importance of ING association with MYST acetyltransferases in controlling cell proliferation, a regulated link that accounts for the reported tumor suppressor activities of these complexes.
authors.affiliation: Laval University Cancer Research Center, Hôtel-Dieu de Québec, Quebec City, Quebec, Canada.
authors.forename: Nikita
authors.initials: N
authors.lastname: Avvakumov
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Lalonde
authors.forename: Nehmé
authors.initials: N
authors.lastname: Saksouk
authors.forename: Eric
authors.initials: E
authors.lastname: Paquet
authors.forename: Karen C
authors.initials: KC
authors.lastname: Glass
authors.forename: Anne-Julie
authors.initials: AJ
authors.lastname: Landry
authors.forename: Yannick
authors.initials: Y
authors.lastname: Doyon
authors.forename: Christelle
authors.initials: C
authors.lastname: Cayrou
authors.forename: Geneviève A
authors.initials: GA
authors.lastname: Robitaille
authors.forename: Darren E
authors.initials: DE
authors.lastname: Richard
authors.forename: Xiang-Jiao
authors.initials: XJ
authors.lastname: Yang
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Kutateladze
authors.forename: Jacques
authors.initials: J
authors.lastname: Côté
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D017434:Protein Structure, Tertiary; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism; D054462:p21-Activated Kinases / Q000737:chemistry / Q000378:metabolism
chemical_list: D006657:Histones; D025521:Tumor Suppressor Proteins; D051548:Histone Acetyltransferases; C496553:KAT7 protein, human; C515903:PAK1 protein, human; D054462:p21-Activated Kinases