title: 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 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.
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors.forename: Shane
authors.initials: S
authors.lastname: McManus
authors.forename: Anja
authors.initials: A
authors.lastname: Ebert
authors.forename: Giorgia
authors.initials: G
authors.lastname: Salvagiotto
authors.forename: Jasna
authors.initials: J
authors.lastname: Medvedovic
authors.forename: Qiong
authors.initials: Q
authors.lastname: Sun
authors.forename: Ido
authors.initials: I
authors.lastname: Tamir
authors.forename: Markus
authors.initials: M
authors.lastname: Jaritz
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tagoh
authors.forename: Meinrad
authors.initials: M
authors.lastname: Busslinger
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D055879:Gene Knock-In Techniques; D018390:Gene Targeting / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D002843:Chromatin; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; C497282:Pax5 protein, mouse