title: Epigenetic Regulation of the Blimp-1 Gene (Prdm1) in B Cells Involves Bach2 and Histone Deacetylase 3.
abstract: B lymphocyte-induced maturation protein 1 (Blimp-1) encoded by Prdm1 is a master regulator of plasma cell differentiation. The transcription factor Bach2 represses Blimp-1 expression in B cells to stall terminal differentiation, by which it supports reactions such as class switch recombination of the antibody genes. We found that histones H3 and H4 around the Prdm1 intron 5 Maf recognition element were acetylated at higher levels in X63/0 plasma cells expressing Blimp-1 than in BAL17 mature B cells lacking its expression. Conversely, methylation of H3-K9 was lower in X63/0 cells than BAL17 cells. Purification of the Bach2 complex in BAL17 cells revealed its interaction with histone deacetylase 3 (HDAC3), nuclear co-repressors NCoR1 and NCoR2, transducin β-like 1X-linked (Tbl1x), and RAP1-interacting factor homolog (Rif1). Chromatin immunoprecipitation confirmed the binding of HDAC3 and Rif1 to the Prdm1 locus. Reduction of HDAC3 or NCoR1 expression by RNA interference in B cells resulted in an increased Prdm1 mRNA expression. Bach2 is suggested to cooperate with HDAC3-containing co-repressor complexes in B cells to regulate the stage-specific expression of Prdm1 by writing epigenetic modifications at the Prdm1 locus.
authors.affiliation: From the Department of Biochemistry and the Department of Pediatric Surgery, Tohoku University Graduate School of Medicine, Seiryo-machi 1-1, Sendai 980-0874.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: From the Department of Biochemistry and CREST, Japan Science and Technology Agency, Seiryo-machi 2-1, Sendai 980-8575.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Muto
authors.affiliation: From the Department of Biochemistry and CREST, Japan Science and Technology Agency, Seiryo-machi 2-1, Sendai 980-8575.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shima
authors.affiliation: From the Department of Biochemistry and Center for Regulatory Epigenome and Diseases,Tohoku University Graduate School of Medicine, Seiryo-machi 2-1, Sendai 980-8575.
authors.forename: Yasutake
authors.initials: Y
authors.lastname: Katoh
authors.affiliation: From the Department of Biochemistry and CREST, Japan Science and Technology Agency, Seiryo-machi 2-1, Sendai 980-8575.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sax
authors.affiliation: From the Department of Biochemistry and.
authors.forename: Shinya
authors.initials: S
authors.lastname: Tajima
authors.affiliation: From the Department of Biochemistry and.
authors.forename: Andrey
authors.initials: A
authors.lastname: Brydun
authors.affiliation: the Radiation Biology Center, Kyoto University, Kyoto 606-8501.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ikura
authors.affiliation: Tokyo Metropolitan Institute of Medical Sciences, Kamikitazawa 1-6, Tokyo 156-8506, and.
authors.forename: Naoko
authors.initials: N
authors.lastname: Yoshizawa
authors.affiliation: Tokyo Metropolitan Institute of Medical Sciences, Kamikitazawa 1-6, Tokyo 156-8506, and.
authors.forename: Hisao
authors.initials: H
authors.lastname: Masai
authors.affiliation: the Japanese Foundation for Cancer Research, Cancer Institute, Ariake 3-10-6, Tokyo 135-8550, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hoshikawa
authors.affiliation: the Japanese Foundation for Cancer Research, Cancer Institute, Ariake 3-10-6, Tokyo 135-8550, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Noda
authors.affiliation: the Department of Pediatric Surgery, Tohoku University Graduate School of Medicine, Seiryo-machi 1-1, Sendai 980-0874.
authors.forename: Masaki
authors.initials: M
authors.lastname: Nio
authors.affiliation: From the Department of Biochemistry and CREST, Japan Science and Technology Agency, Seiryo-machi 2-1, Sendai 980-8575.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ochiai
authors.affiliation: From the Department of Biochemistry and CREST, Japan Science and Technology Agency, Seiryo-machi 2-1, Sendai 980-8575, Center for Regulatory Epigenome and Diseases,Tohoku University Graduate School of Medicine, Seiryo-machi 2-1, Sendai 980-8575, igarashi@med.tohoku.ac.jp.
authors.forename: Kazuhiko
authors.identifier: http://orcid.org/0000-0002-2470-2475
authors.initials: K
authors.lastname: Igarashi
mesh_terms: D000107:Acetylation; D000818:Animals; D001402:B-Lymphocytes; D050976:Basic-Leucine Zipper Transcription Factors / Q000502:physiology*; D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D057809:HEK293 Cells; D006655:Histone Deacetylases / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D056971:Nuclear Receptor Co-Repressor 1 / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D034501:Telomere-Binding Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000099186:Histone Deacetylase 3
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D006655:Histone Deacetylases; D006657:Histones; D056971:Nuclear Receptor Co-Repressor 1; D000074462:Positive Regulatory Domain I-Binding Factor 1; D034501:Telomere-Binding Proteins; D014157:Transcription Factors; D000099186:Histone Deacetylase 3; C102109:Bach2 protein, mouse; C539128:Ncor1 protein, mouse; C513258:Prdm1 protein, mouse; C492748:Rif1 protein, mouse
keywords: B cells; acetylation; epigenetics; gene regulation; histone; methylation; plasma cells; transcription factor