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Publication : The transcription factor Pax5 regulates its target genes by recruiting chromatin-modifying proteins in committed B cells.

First Author  McManus S Year  2011
Journal  EMBO J Volume  30
Issue  12 Pages  2388-404
PubMed ID  21552207 Mgi Jnum  J:173158
Mgi Id  MGI:5013490 Doi  10.1038/emboj.2011.140
Citation  McManus S, et al. (2011) The transcription factor Pax5 regulates its target genes by recruiting chromatin-modifying proteins in committed B cells. EMBO J 30(12):2388-404
abstractText  Pax5 is a critical regulator of B-cell commitment. Here, we identified direct Pax5 target genes by streptavidin-mediated ChIP-chip analysis of pro-B cells expressing in vivo biotinylated Pax5. By binding to promoters and enhancers, Pax5 directly regulates the expression of multiple transcription factor, cell surface receptor and signal transducer genes. One of the newly identified enhancers was shown by transgenic analysis to confer Pax5-dependent B-cell-specific activity to the Nedd9 gene controlling B-cell trafficking. Profiling of histone modifications in Pax5-deficient and wild-type pro-B cells demonstrated that Pax5 induces active chromatin at activated target genes, while eliminating active chromatin at repressed genes in committed pro-B cells. Pax5 rapidly induces these chromatin and transcription changes by recruiting chromatin-remodelling, histone-modifying and basal transcription factor complexes to its target genes. These data provide novel insight into the regulatory network and epigenetic regulation, by which Pax5 controls B-cell commitment.
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