YY1 binds to the E3′ enhancer and inhibits the expression of the immunoglobulin κ gene via epigenetic modifications

The rearrangement and expression of immunoglobulin genes are regulated by enhancers and their binding transcriptional factors that activate or suppress the activities of the enhancers. The immunoglobulin kappa (Ig kappa) gene locus has three important enhancers: the intrinsic enhancer (Ei), 3 ' enhancer (E3 '), and distal enhancer (Ed). Ei and E3 ' are both required for Ig kappa gene rearrangement during early stages of B-cell development, whereas optimal expression of the rearranged Ig kappa gene relies on both E3 ' and Ed. The transcription factor YY1 affects the expression of many genes involved in B-cell development, probably by mediating interactions between their enhancers and promoters. Herein, we found that YY1 binds to the E3MODIFIER LETTER PRIME enhancer and suppresses Ig kappa expression in B lymphoma cells by epigenetically modifying the enhancer. Knocking down YY1 enhanced Ig kappa expression, which was associated with increased levels of E2A (encoded by the TCF3 gene) and its binding to the E3MODIFIER LETTER PRIME enhancer. Moreover, in germinal centre B cells and plasma cells, YY1 expression was reversely associated with Ig kappa levels, implying that YY1 might facilitate antibody affinity maturation in germinal centre B cells through the transient attenuation of Ig kappa expression.