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

Fang Wei, Kristina Zaprazna, Junwen Wang, Michael L. Atchison

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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 (Igκ) intron and 3′ enhancers. At the Igκ 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 Igκ and Igλ 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.

Original languageEnglish (US)
Pages (from-to)4612-4622
Number of pages11
JournalMolecular and Cellular Biology
Volume29
Issue number17
DOIs
StatePublished - Sep 2009
Externally publishedYes

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Germinal Center
B-Lymphocytes
Gene Expression
DNA
Binding Sites
Genes
Chromatin Immunoprecipitation
Genetic Promoter Regions
Introns
Immunoglobulins
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

PU.1 can recruit BCL6 to DNA to repress gene expression in germinal center B cells. / Wei, Fang; Zaprazna, Kristina; Wang, Junwen; Atchison, Michael L.

In: Molecular and Cellular Biology, Vol. 29, No. 17, 09.2009, p. 4612-4622.

Research output: Contribution to journalArticle

Wei, Fang ; Zaprazna, Kristina ; Wang, Junwen ; Atchison, Michael L. / PU.1 can recruit BCL6 to DNA to repress gene expression in germinal center B cells. In: Molecular and Cellular Biology. 2009 ; Vol. 29, No. 17. pp. 4612-4622.
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