title: Identification of Pax5 target genes in early B cell differentiation.
abstract: The transcription factor Pax5 is essential for B cell commitment in the mouse, where it represses lineage-inappropriate gene expression while simultaneously activating the B cell gene expression program. In this study we have performed a global gene expression screen of wild-type and Pax5-deficient pro-B cells in an attempt to identify the crucial Pax5 targets in early B lymphopoiesis. These studies have identified 109 Pax5 targets comprising 61% activated and 39% repressed genes. Interestingly, Pax5 directly regulates the genes encoding a number of transcription factors that are required at the pre-B cell stage of differentiation, including Irf8, Spib, and Ikzf3 (Aiolos), suggesting that a key function of Pax5 is to activate secondary transcription factors that further reinforce the B cell program. Pax5 is also required for the expression of many genes known to be involved in adhesion and signaling, indicating that Pax5 modulates the homing and or migration properties of B cell progenitors. Finally, Pax5 also represses a cohort of genes that are involved in multiple biological processes, many of which are not typically associated with B cells. These include the repression of the adhesion molecule Embigin, which is expressed in bone marrow progenitors, T cells, and myeloid cells but is specifically repressed by Pax5 in B cells.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
authors.forename: Clare
authors.initials: C
authors.lastname: Pridans
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Holmes
authors.forename: Matthew
authors.initials: M
authors.lastname: Polli
authors.forename: James M
authors.initials: JM
authors.lastname: Wettenhall
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Dakic
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Corcoran
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Smyth
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Nutt
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D020411:Oligonucleotide Array Sequence Analysis; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D014157:Transcription Factors