Epigenetic Regulation of the Blimp-1 Gene (Prdm1) in B Cells Involves Bach2 and Histone Deacetylase 3

• Published in: The Journal of biological chemistry Vol. 291; no. 12; pp. 6316 - 6330
• Main Authors: Tanaka, Hiromu, Muto, Akihiko, Shima, Hiroki, Katoh, Yasutake, Sax, Nicolas, Tajima, Shinya, Brydun, Andrey, Ikura, Tsuyoshi, Yoshizawa, Naoko, Masai, Hisao, Hoshikawa, Yutaka, Noda, Tetsuo, Nio, Masaki, Ochiai, Kyoko, Igarashi, Kazuhiko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.03.2016; American Society for Biochemistry and Molecular Biology
• Subjects: Acetylation; Animals; B cells; B-Lymphocytes; Basic-Leucine Zipper Transcription Factors - physiology; Cell Line, Tumor; Epigenesis, Genetic; epigenetics; Gene Regulation; Gene Silencing; HEK293 Cells; histone; Histone Deacetylases - physiology; Histones - metabolism; Humans; methylation; Mice; Nuclear Receptor Co-Repressor 1 - metabolism; plasma cells; Positive Regulatory Domain I-Binding Factor 1; Promoter Regions, Genetic; Protein Processing, Post-Translational; Telomere-Binding Proteins - metabolism; transcription factor; Transcription Factors - genetics; Transcription Factors - metabolism; acetylation; transcription factor; gene regulation; methylation; histone; B cells; plasma cells; epigenetics
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M116.713842

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.