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Molecular and Cellular Biology, April 2000, p. 2592-2603, Vol. 20, No. 7
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.
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
*
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.
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