The PU.1 binding site is a cis-element that regulates pro-B/pre-B specificity of Vkappa-Jkappa joining.

Abstract

We have previously shown that the PU.1 binding motif (GAG GAA) in the 3'-enhancer region in the Ig kappa gene is responsible for the negative regulation of tissue (B/T)-specific Vkappa-Jkappa joining. Here we report that the PU.1 binding site also regulates the stage (pro-B/pre-B) specificity of Vkappa-Jkappa joining. In the substrate with base substitutions in the PU.1 binding motif, recombination took place in both pro-B (B220dull/CD43+) and pre-B (B220dull/CD43-) cells. In the transcriptional regulation, the PU.1 motif acts in a positive manner cooperatively with the nuclear factor-EM5 (or PIP) motif (GAAAAC), which is located 2 bp downstream from the PU.1 motif. Interestingly, base substitutions in the nuclear factor EM5 (PIP) motif did not affect the pro-B/pre-B specificity of Vkappa-Jkappa joining. Thus, the PU.1 motif regulates both temporal and tissue-specific rearrangements, while nuclear factor-EM5 is not involved in the regulation of Ig kappa recombination.

EBF1, PAX5, and MYC: regulation on B cell development and association with hematologic neoplasms

“…It was demonstrated that EBF1 is necessary not only for the survival, proliferation, and signaling of pro-B cells and peripheral B-cell subsets (such as B1 cells and marginal zone B cells) but also for germinal center formation and class switch recombination (30). Ikaros and PU.1 contribute to lymphoid progenitor cell differentiation into pro-B cells, and this process is blocked when these two TFs are deficient (31)(32)(33)(34). The overexpression of EBF1 induces Ikaros-KO Lin-Sca1 hi c-Kit hi cells to differentiate into pro-B cells (35).…”