Transcriptional repression by blimp-1 (PRDI-BF1) involves recruitment of histone deacetylase.
B-lymphocyte-induced maturation protein (Blimp-1) is a transcriptional repressor that is considered to be a master regulator of terminal B-cell development because it is sufficient to trigger differentiation in the BCL(1)-cell model. Transcription of the c-myc gene is repressed by Blimp-1 during B-cell differentiation. In this study, we have explored the mechanism by which Blimp-1 represses transcription by using Gal4-fusion protein assays and assays 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 independent of the adjacently bound activator YY1. Blimp-1 contains two regions that independently associate with histone deacetylase (HDAC) and endogenous Blimp-1 in nuclear extracts binds in vitro to the c-myc Blimp-1 site in a complex containing HDAC. The functional importance of recruiting HDAC for Blimp-1-dependent repression of c-myc transcription is supported by two experiments. First, the HDAC inhibitor tricostatin A inhibits Blimp-1-dependent repression in cotransfection assays. Second, a chromatin immunoprecipitation assay shows that expression of Blimp-1 causes deacetylation of histone H3 associated with the c-myc promoter, and this deacetylation depends on the Blimp-1 binding site in the c-myc promoter.
Yu
J
J
Departments of Biochemistry and Molecular Biophysics, Cellular and Molecular Studies, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Angelin-Duclos
C
C
Greenwood
J
J
Liao
J
J
Calame
K
K
D000107:Acetylation; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D050981:Erythroid-Specific DNA-Binding Factors; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D050986:YY1 Transcription Factor
D002843:Chromatin; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D050981:Erythroid-Specific DNA-Binding Factors; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D006657:Histones; D006877:Hydroxamic Acids; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C087042:PRDM1 protein, human; C012589:trichostatin A; D000074462:Positive Regulatory Domain I-Binding Factor 1; D006655:Histone Deacetylases