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

Robert Wuerffel , Lili Wang , Fernando Grigera , John Manis , Erik Selsing , Thomas Perlot , Frederick W Alt , Michel Cogné (1, 2) , Eric Pinaud (2) , Amy L Kenter

1 UNILIM - Université de Limoges
2 PMRIL - Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations

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 Emicro and 3'Ealpha enhancers were in close spatial proximity, forming a unique chromosomal loop configuration. B cell activation led to recruitment of the germline transcript (GLT) promoters to the Emicro:3'Ealpha complex in a cytokine-dependent fashion. This structure facilitated S-S synapsis because Smicro was proximal to Emicro and a downstream S region was corecruited with the targeted GLT promoter to Emicro:3'Ealpha. We propose that GLT promoter association with the Emicro:3'Ealpha 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 GLT expression and may serve to guard against spurious chromosomal translocations.

Domaines: Immunologie

Robert Wuerffel, Lili Wang, Fernando Grigera, John Manis, Erik Selsing, et al.. S-S synapsis during class switch recombination is promoted by distantly located transcriptional elements and activation-induced deaminase.. Immunity, 2007, 27 (5), pp.711-22. ⟨10.1016/j.immuni.2007.09.007⟩. ⟨hal-00363968⟩