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Molecular and Cellular Biology, April 2000, p. 2592-2603, Vol. 20, No. 7
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Transcriptional Repression by Blimp-1 (PRDI-BF1) Involves Recruitment of Histone Deacetylase

Jin Yu,1 Cristina Angelin-Duclos,2 Jessica Greenwood,3 Jerry Liao,2 and Kathryn Calame1,2,3,*

Departments of Biochemistry and Molecular Biophysics1 and Microbiology2 and the Integrated Program in Biophysical, Cellular and Molecular Studies,3 Columbia University College of Physicians and Surgeons, New York, New York 10032

Received 1 September 1999/Returned for modification 12 October 1999/Accepted 13 January 2000

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 BCL1-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.

* Corresponding author. Mailing address: Dept. of Microbiology, Columbia Univ. College of Physicians & Surgeons, 1208 Hammer Hlth. Sci. Ctr., MB 122, 701 West 168th St., New York, NY 10032. Phone: (212) 305-3504. Fax: (212) 305-1468. E-mail: KLC1{at}columbia.edu.

Molecular and Cellular Biology, April 2000, p. 2592-2603, Vol. 20, No. 7
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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