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Molecular and Cellular Biology, September 2009, p. 4612-4622, Vol. 29, No. 17
0270-7306/09/$08.00+0     doi:10.1128/MCB.00234-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

PU.1 Can Recruit BCL6 to DNA To Repress Gene Expression in Germinal Center B Cells {triangledown}

Fang Wei,1 Kristina Zaprazna,1 Junwen Wang,2 and Michael L. Atchison1*

Department of Animal Biology and Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, Pennsylvania 19104,1 Department of Biochemistry, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China2

Received 20 February 2009/ Returned for modification 2 April 2009/ Accepted 22 June 2009

BCL6 is a transcriptional repressor crucial for germinal center formation. BCL6 represses transcription by a variety of mechanisms by binding to specific DNA sequences or by recruitment to DNA by protein interactions. We found that BCL6 can inhibit activities of the immunoglobulin kappa (Ig{kappa}) intron and 3' enhancers. At the Ig{kappa} 3' enhancer, BCL6 repressed enhancer activity through the PU.1 binding site. We found that BCL6 physically interacted with PU.1 in vivo and in vitro, and the results of sequential chromatin immunoprecipitation assays and transient-expression assays suggested that BCL6 recruitment to the Ig{kappa} and Ig{lambda} 3' enhancers occurred via PU.1 interaction. By computational studies, we identified genes that are repressed in germinal center cells and whose promoters contain conserved PU.1 binding sites in mouse and human. We found that many of these promoters bound to both PU.1 and BCL6 in vivo. In addition, BCL6 knockdown resulted in increased expression of a subset of these genes, demonstrating that BCL6 is involved in their repression. The recruitment of BCL6 to promoter regions by PU.1 represents a new regulatory mechanism that expands the number of genes regulated by this important transcriptional repressor.

* Corresponding author. Mailing address: School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104. Phone: (215) 898-6428. Fax: (215) 573-5189. E-mail: atchison{at}vet.upenn.edu

{triangledown} Published ahead of print on 29 June 2009.

Molecular and Cellular Biology, September 2009, p. 4612-4622, Vol. 29, No. 17
0270-7306/09/$08.00+0     doi:10.1128/MCB.00234-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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