Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 291, Issue 12, Pages 6316-6330Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M116.713842
Keywords
acetylation; epigenetics; gene regulation; histone; transcription factor; B cells; methylation; plasma cells
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Funding
- Japan Society for the Promotion of Science [15H02506, 24390066, 21249014, 17054028, 25460352, 24790271]
- Network Medicine Global COE Program from the Ministry of Education, Culture, Sport, Science and Technology of Japan
- Takeda Foundation and Astellas Foundation for Research on Metabolic Disorders
- Grants-in-Aid for Scientific Research [17054028, 15K12203, 26251004, 26281020, 25460352, 21249014, 15K07164, 24790271, 24390066] Funding Source: KAKEN
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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 -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.
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