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The transcription factor Pax5 regulates its target genes by recruiting chromatin-modifying proteins in committed B cells
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The transcription factor Pax5 regulates its target genes by recruiting chromatin-modifying proteins in committed B cells
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Journal Article
The transcription factor Pax5 regulates its target genes by recruiting chromatin-modifying proteins in committed B cells
2011
Overview
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.
The mechanism of Pax5‐mediated gene activation and repression during early B‐cell development is unclear. This study identifies Pax5‐binding sites in pro‐B cells and the changes in chromatin modifications induced by the recruitment of chromatin‐modifying and transcription factors.
Publisher
John Wiley & Sons, Ltd,Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
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