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The mechanism of repression of the myeloid‐specific c ‐fms gene by Pax5 during B lineage restriction
Author(s) -
Tagoh Hiromi,
Ingram Richard,
Wilson Nicola,
Salvagiotto Giorgia,
Warren Alan J,
Clarke Deborah,
Busslinger Meinrad,
Bonifer Constanze
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600997
Subject(s) - biology , psychological repression , genetics , lineage (genetic) , mechanism (biology) , pax5 , gene , microbiology and biotechnology , transcription factor , gene expression , philosophy , epistemology
The transcription factor Pax5 (BSAP) is required for the expression of a B‐cell‐specific genetic program and for B‐cell differentiation, and also to suppress genes of alternative lineages. The molecular mechanism by which repression of myeloid genes occurs during early B‐lineage restriction is unknown and in this study we addressed this question. One of the genes repressed by Pax5 in B cells is the colony‐stimulating factor receptor 1 gene ( csf1r or c ‐fms ). We examined the changes in chromatin caused by Pax5 activity, and we show that Pax5 is directly recruited to c ‐fms resulting in the rapid loss of RNA polymerase II binding, followed by loss of transcription factor binding and DNaseI hypersensitivity at all cis ‐regulatory elements. We also show that Pax5 targets the basal transcription machinery of c ‐fms by interacting with a binding site within the major transcription start sites. Our results support a model by which Pax5 does not lead to major alterations in chromatin modification, but inhibits transcription by interfering with the action of myeloid transcription factors.