Elucidation of IgH 3′ region regulatory role during class switch recombination via germline deletion

Alexis Saintamand, Pauline Rouaud, Faten Saad, Géraldine Rios, Michel Cogné and Yves Denizot ()
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Alexis Saintamand: Université de Limoges, CRIBL, UMR 7276
Pauline Rouaud: Université de Limoges, CRIBL, UMR 7276
Faten Saad: Université de Limoges, CRIBL, UMR 7276
Géraldine Rios: CNRS et Université de Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 6097
Michel Cogné: Université de Limoges, CRIBL, UMR 7276
Yves Denizot: Université de Limoges, CRIBL, UMR 7276

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract In mature B cells, class switch recombination (CSR) replaces the expressed constant Cμ gene with a downstream CH gene. How the four transcriptional enhancers of the IgH 3′ regulatory region (3′RR) control CSR remains an open question. We have investigated IgG1 CSR in 3′RR-deficient mice. Here we show that the 3′RR enhancers target the Sγ1 acceptor region (and poorly the Sμ donor region) by acting on epigenetic marks, germline transcription, paused RNA Pol II recruitment, R loop formation, AID targeting and double-strand break generation. In contrast, location and diversity of Sμ-Sγ1 junctions are not affected by deletion of the 3′RR enhancers. Thus, the 3′RR controls the first steps of CSR by priming the S acceptor region but is not implicated in the choice of the end-joining pathway.

Date: 2015
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DOI: 10.1038/ncomms8084

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