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

J Biol Chem. 2016 Mar 18;291(12):6316-30. doi: 10.1074/jbc.M116.713842. Epub 2016 Jan 19.

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.

Keywords: B cells; acetylation; epigenetics; gene regulation; histone; methylation; plasma cells; transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • B-Lymphocytes
  • Basic-Leucine Zipper Transcription Factors / physiology*
  • Cell Line, Tumor
  • Epigenesis, Genetic
  • Gene Silencing*
  • HEK293 Cells
  • Histone Deacetylases / physiology*
  • Histones / metabolism
  • Humans
  • Mice
  • Nuclear Receptor Co-Repressor 1 / metabolism
  • Positive Regulatory Domain I-Binding Factor 1
  • Promoter Regions, Genetic
  • Protein Processing, Post-Translational
  • Telomere-Binding Proteins / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Bach2 protein, mouse
  • Basic-Leucine Zipper Transcription Factors
  • Histones
  • Ncor1 protein, mouse
  • Nuclear Receptor Co-Repressor 1
  • Prdm1 protein, mouse
  • Rif1 protein, mouse
  • Telomere-Binding Proteins
  • Transcription Factors
  • Positive Regulatory Domain I-Binding Factor 1
  • Histone Deacetylases
  • histone deacetylase 3