YY1-mediated enhancer-promoter communication in the immunoglobulin μ locus is regulated by MSL/MOF recruitment

The rearrangement and expression of the immunoglobulin mu heavy chain (Igh) Igh ) gene require communication of the intragenic E mu and 30 0 regulatory region (RR) enhancers with the variable (VH) H ) gene promoter. E mu binding of the transcription factor YY1 has been implicated in enhancer-promoter communication, but the YY1 protein network remains obscure. By analyzing the comprehensive proteome of the 1-kb E mu wild-type enhancer and that of E mu lacking the YY1 binding site, we identified the male-specific lethal (MSL)/MOF complex as a component of the YY1 protein network. We found that MSL2 recruitment depends on YY1 and that gene knockout of Msl2 in primary pre-B cells reduces mu gene expression and chromatin looping of E mu to the 30 0 RR enhancer and VH H promoter. Moreover, Mof heterozygosity in mice impaired mu expression and early B cell differentiation. Together, these data suggest that the MSL/MOF complex regulates Igh gene expression by augmenting YY1-mediated enhancer-promoter communication.