HoxC4 binds to the Aicda promoter to induce AID expression class switch DNA recombination and somatic hypermutation

摘要

AID is critical for immunoglobulin class switch DNA recombination (CSR) and somatic hypermutation (SHM). Here we showed that AID expression was induced by the HoxC4 homeodomain transcription factor, which bound to a highly conserved HoxC4-Oct site in the Aicda promoter. This site functioned in synergy with a conserved Sp-NF-κB-binding site. HoxC4 was preferentially expressed in germinal center B cells and was upregulated by CD154:CD40 engagement, lipopolysaccharide and interleukin-4. HoxC4 deficiency resulted in impaired CSR and SHM, due to decreased AID expression and not other putative HoxC4-dependent activity. Enforced expression of AID in Hoxc4^−/− B cells fully restored CSR. Thus, HoxC4 directly activates the Aicda promoter, thereby inducing AID expression, CSR and SHM.