The mechanism of repression of the myeloid-specific c-fms gene by Pax5 during B lineage restriction
Hiromi Tagoh,Richard Ingram,Nicola K. Wilson,Giorgia Salvagiotto,Alan J. Warren,Alan J. Warren,Deborah Clarke,Meinrad Busslinger,Constanze Bonifer +8 more
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TLDR
The 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.Abstract:
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.read more
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Dissertation
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Journal ArticleDOI
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Dissertation
Role of Histone Deacetylase HDAC7 in B Lymphocyte Biology
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References
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Commitment to the B-lymphoid lineage depends on the transcription factor Pax5.
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Journal ArticleDOI
Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects.
Xuming Dai,Gregory R. Ryan,Andrew J. Hapel,Melissa G. Dominguez,Robert G. Russell,Sara Kapp,Vonetta Sylvestre,E. Richard Stanley +7 more
TL;DR: The results indicate that all of the effects of CSF-1 are mediated via the CSf-1R, but that subtle effects of the CS fms proto-oncogene could result from its CS F-1-independent activation.
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