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Publication : PU.1 can recruit BCL6 to DNA to repress gene expression in germinal center B cells.

First Author  Wei F Year  2009
Journal  Mol Cell Biol Volume  29
Issue  17 Pages  4612-22
PubMed ID  19564417 Mgi Jnum  J:152615
Mgi Id  MGI:4359318 Doi  10.1128/MCB.00234-09
Citation  Wei F, et al. (2009) PU.1 can recruit BCL6 to DNA to repress gene expression in germinal center B cells. Mol Cell Biol 29(17):4612-22
abstractText  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 (Igkappa) intron and 3' enhancers. At the Igkappa 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 Igkappa and Iglambda 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.
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