Transcriptional repression by Blimp-1 (PRDI-BF1) involves recruitment of histone deacetylase

B-lymphocyte-induced maturation protein (Blimp-1) is a transcriptional repr essor that is considered to be a master regulator of terminal B-cell develo pment because it is sufficient to trigger differentiation in the BCL1-cell model. Transcription of the c-myc gene is repressed by Blimp-1 during B-cel l differentiation. In this study, we have explored the mechanism by which B limp-1 represses transcription by using Gat 1-fusion protein assays and ass ays in which Blimp-1 represses the natural c-myc promoter. The results show that Blimp-1 represses the c-myc promoter by an active mechanism that is i ndependent of the adjacently bound activator YY1, Blimp-1 contains two regi ons that independently associate with histone deacetylase (HDAC) and endoge nous Blimp-1 in nuclear extracts binds in vitro to the c-myc Blimp-1 site i n a complex containing HDAC. The functional importance of recruiting HDAC f or Blimp-1-dependent repression of c-myc transcription is supported by two experiments. First, the HDAC inhibitor tricostatin A inhibits Blimp-1-depen dent repression in cotransfection assays. Second, a chromatin immunoprecipi tation assay shows that expression of Blimp-1 causes deacetylation of histo ne H3 associated with the c-myc promoter, and this deacetylation depends on the Blimp-1 binding site in the c-myc promoter.