CFP1 promotes B cell class switch recombination through the regulation of S region germline transcription and proliferation.

Antibody class switch recombination (CSR) is a transcription-coupled process involving targeted DNA deamination and coordinated DNA repair in the immunoglobulin heavy-chain (Igh) constant gene locus. The epigenetic regulation mechanism of CSR is incompletely understood. Here, we show that the histone methyltransferase component CFP1 is critically required for CSR in activated B cells. Although CFP1 ablation does not negatively affect Aicda expression or DSB repair, it impairs switch (S) region germline transcription and disrupts AID activity-mediated hypermutation. CFP1 deficiency reshapes the global H3K4me3 landscape at promoters of cell cycle-related genes, including Pcna, leading to its mis-regulation, impaired cell proliferation, and genome instabilities. Therefore, CFP1 coordinates chromatin states and transcription to ensure effective CSR via epigenetic regulation.