Role of Ikaros in Early B-cell Development: Studies of IkZnF1-/- and IkZnF4-/- mutant mice

Ikaros is a zinc finger (ZnF) transcription factor critical for B-cell development. The C2H2 zinc finger is the most prevalent DNA-binding motif in the mammalian proteome, with DNA-binding domains usually containing more tandem fingers than are needed for stable sequence-specific DNA recognition. To examine the reason for the frequent presence of multiple zinc fingers, we generated mice lacking finger 1 or finger 4 of the 4-finger DNA-binding domain of Ikaros (Schjerven et al., Nat Immunol, 2013; PMID: 24013668). Each mutant strain exhibited a specific subset of the phenotypes observed with Ikaros null mice, and revealed that different subsets of fingers within multi-finger transcription factors can regulate distinct target genes and biological functions. We here study the effect of these mutants on early B-cell development in the bone marrow (BM) with transcriptome profiling of sorted proB-cells (Hardy fractions B+C+C') from BM of wt and the two ZnF mutants (this GEO submission: RNA-Seq). Overall design: RNA-Seq from sorted primary proB cells of combined Hardy Fractions B+C+C' (BC), comparing wt, Ikaros-ZnF1-/- mutant and Ikaros-ZnF4-/- mutant (B220+, CD19+, IgM-, CD24+, BP1+/-).