title: The Chromatin Regulator BRPF3 Preferentially Activates the HBO1 Acetyltransferase but Is Dispensable for Mouse Development and Survival.
abstract: To interpret epigenetic information, chromatin readers utilize various protein domains for recognition of DNA and histone modifications. Some readers possess multidomains for modification recognition and are thus multivalent. Bromodomain- and plant homeodomain-linked finger-containing protein 3 (BRPF3) is such a chromatin reader, containing two plant homeodomain-linked fingers, one bromodomain and a PWWP domain. However, its molecular and biological functions remain to be investigated. Here, we report that endogenous BRPF3 preferentially forms a tetrameric complex with HBO1 (also known as KAT7) and two other subunits but not with related acetyltransferases such as MOZ, MORF, TIP60, and MOF (also known as KAT6A, KAT6B, KAT5, and KAT8, respectively). We have also characterized a mutant mouse strain with a lacZ reporter inserted at the Brpf3 locus. Systematic analysis of β-galactosidase activity revealed dynamic spatiotemporal expression of Brpf3 during mouse embryogenesis and high expression in the adult brain and testis. Brpf3 disruption, however, resulted in no obvious gross phenotypes. This is in stark contrast to Brpf1 and Brpf2, whose loss causes lethality at E9.5 and E15.5, respectively. In Brpf3-null mice and embryonic fibroblasts, RT-quantitative PCR uncovered no changes in levels of Brpf1 and Brpf2 transcripts, confirming no compensation from them. These results indicate that BRPF3 forms a functional tetrameric complex with HBO1 but is not required for mouse development and survival, thereby distinguishing BRPF3 from its paralogs, BRPF1 and BRPF2.
authors.affiliation: From the Rosalind and Morris Goodman Cancer Research Center, Departments of Biochemistry and Medicine, McGill University, Montreal, Quebec H3A 1A3, Canada.
authors.forename: Kezhi
authors.initials: K
authors.lastname: Yan
authors.affiliation: From the Rosalind and Morris Goodman Cancer Research Center, Medicine, McGill University, Montreal, Quebec H3A 1A3, Canada.
authors.forename: Linya
authors.initials: L
authors.lastname: You
authors.affiliation: From the Rosalind and Morris Goodman Cancer Research Center.
authors.forename: Cindy
authors.initials: C
authors.lastname: Degerny
authors.affiliation: From the Rosalind and Morris Goodman Cancer Research Center, Medicine, McGill University, Montreal, Quebec H3A 1A3, Canada.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ghorbani
authors.affiliation: From the Rosalind and Morris Goodman Cancer Research Center.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: the State Key Laboratory of Reproductive Medicine, Research Center for Bone and Stem Cells, Department of Human Anatomy, Nanjing Medical University, Nanjing 210029, China, and.
authors.forename: Lulu
authors.initials: L
authors.lastname: Chen
authors.affiliation: From the Rosalind and Morris Goodman Cancer Research Center, Medicine, McGill University, Montreal, Quebec H3A 1A3, Canada.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: the State Key Laboratory of Reproductive Medicine, Research Center for Bone and Stem Cells, Department of Human Anatomy, Nanjing Medical University, Nanjing 210029, China, and.
authors.forename: Dengshun
authors.initials: D
authors.lastname: Miao
authors.affiliation: From the Rosalind and Morris Goodman Cancer Research Center, Departments of Biochemistry and Medicine, McGill University, Montreal, Quebec H3A 1A3, Canada, the McGill University Health Center, Montreal, Quebec H3A 1A3, Canada xiang-jiao.yang@mcgill.ca.
authors.forename: Xiang-Jiao
authors.initials: XJ
authors.lastname: Yang
mesh_terms: D000818:Animals; D020964:Embryo Loss / Q000201:enzymology / Q000235:genetics; D004622:Embryo, Mammalian / Q000201:enzymology*; D047108:Embryonic Development; D057809:HEK293 Cells; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*
chemical_list: D009097:Multienzyme Complexes; D051548:Histone Acetyltransferases; C525638:Kat7 protein, mouse
keywords: chromatin modification; development; epigenetics; gene regulation; mouse genetics