S-S Synapsis during class switch recombination is promoted by distantly located transcriptional elements and activation-induced deaminase

Molecular mechanisms underlying synapsis of activation-induced deaminase (AID)-targeted S regions during class switch recombination (CSR) are poorly understood. By using chromosome conformation capture techniques, we found that in B cells, the E mu and 3'E alpha enhancers were in close spatial proximity, forming a unique chromosomal loop configuration. B cell activa tion led to recruitment of the germline transcript (GLT) promoters to the E mu:3'E alpha complex in a cytokine-dependent fashion. This structure facilitated S-S synapsis because S mu was proximal to Et and a downstream S region was corecruited with the targeted GLT promoter to E mu:3'E alpha. We propose that GILT promoter association with the E mu:3'E alpha complex creates an architectural scaffolding that promotes S-S synapsis during CSR and that these interactions are stabilized by AID. Thus, the S-S synaptosome is formed as a result of the self-organizing transcription system that regulates GILT expression and may serve to guard against spurious chromosomal translocations.