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* The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; and
University of Western Sydney, Richmond, Australia
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a Pfizer Australia Research Fellowship (to S.L.N.), and the National Health and Medical Research Council of Australia.
2 C.P. and M.L.H. contributed equally to this work.
3 Current address: Cambridge Institute for Medical Research, Department of Haematology, Hills Road, Cambridge CB2 OXY, U.K.
4 Address correspondence and reprint requests to Dr. Stephen L. Nutt, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, Australia 3050. E-mail address: nutt{at}wehi.edu.au
5 Abbreviations used in this paper: HSC, hemopoietic stem cell; BM, bone marrow; CLP, common lymphoid progenitor; EMB, Embigin; ER, estrogen receptor; NIA 15k, 15,000 clone mouse cDNA library of National Institute of Aging; Sdc4, syndecan-4.
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