The Justy mutation identifies Gon4-like as a gene that is essential for B lymphopoiesis

Hematopoietic progenitor cells progress through pathways that restrict developmental plasticity and enforce commitment to specific lineages (Laiosa et al., 2006; Brown et al., 2007). These processes coincide with gene expression remodeling as orchestrated by a transcription factor network (Laiosa et al., 2006; Nutt and Kee, 2007). Many DNA-binding components of this network are known, but how these proteins coordinately regulate gene expression is poorly understood. Also, disruption of the hematopoietic transcription factor network is strongly associated with oncogenesis (O’Neil and Look, 2007; Rosenbauer and Tenen, 2007). Thus, further characterizing the mechanisms that control hematopoiesis could provide insights regarding neoplasia in this system. Among hematopoietic developmental pathways, B lymphopoiesis is well defined (Hardy et al., 2007; Welner et al., 2008). During this process, the transcription factors Ikaros, E2A, EBF, and Pax5 likely function to recruit protein complexes that activate B-lineage genes or repress genes associated with other lineages (Ng et al., 2007; Nutt and Kee, 2007). Consistent with this idea, gene activation by EBF and Pax5 involves the chromatin-remodeling complex SWI–SNF, whereas Ikaros or Pax5 can interact with transcriptional corepressors (Eberhard et al., 2000; Koipally and Georgopoulos, 2002; Gao et al., 2009). Interactions between B cell transcription factors and unknown cofactors are CORRESPONDENCE John Colgan: john-colgan@uiowa.edu