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

ABSTRACT: 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 committed 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-remodeling, 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. Analysis of chromatin and TF binding in rag2-/- and pax5-/- rag2-/- pro-B cells. Chip-Chip with 1-3 experiments for each antibody and celltype combination.

ORGANISM(S): Mus musculus  

SUBMITTER: Anja Ebert  Shane McManus   Meinrad Busslinger    

PROVIDER: E-GEOD-28373 | ArrayExpress | 2012-03-29

SECONDARY ACCESSION(S): GSE28373PRJNA139441

REPOSITORIES: GEO, ArrayExpress