Deciphering the importance of the palindromic architecture of the immunoglobulin heavy-chain 3’ regulatory region

Alexis Saintamand, Christelle Vincent-Fabert, Armand Garot, Pauline Rouaud, Zeliha Oruc, Virginie Magnone, Michel Cogné and Yves Denizot ()
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Alexis Saintamand: Université de Limoges, CRIBL, UMR CNRS 7276
Christelle Vincent-Fabert: Université de Limoges, CRIBL, UMR CNRS 7276
Armand Garot: Université de Limoges, CRIBL, UMR CNRS 7276
Pauline Rouaud: Université de Limoges, CRIBL, UMR CNRS 7276
Zeliha Oruc: Université de Limoges, CRIBL, UMR CNRS 7276
Virginie Magnone: CNRS et Université de Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire
Michel Cogné: Université de Limoges, CRIBL, UMR CNRS 7276
Yves Denizot: Université de Limoges, CRIBL, UMR CNRS 7276

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract The IgH 3’ regulatory region (3’RR) controls class switch recombination (CSR) and somatic hypermutation (SHM) in B cells. The mouse 3’RR contains four enhancer elements with hs1,2 flanked by inverted repeated sequences and the centre of a 25-kb palindrome bounded by two hs3 enhancer inverted copies (hs3a and hs3b). hs4 lies downstream of the palindrome. In mammals, evolution maintained this unique palindromic arrangement, suggesting that it is functionally significant. Here we report that deconstructing the palindromic IgH 3’RR strongly affects its function even when enhancers are preserved. CSR and IgH transcription appear to be poorly dependent on the 3’RR architecture and it is more or less preserved, provided 3’RR enhancers are present. By contrast, a ‘palindromic effect’ significantly lowers VH germline transcription, AID recruitment and SHM. In conclusion, this work indicates that the IgH 3’RR does not simply pile up enhancer units but also optimally exposes them into a functional architecture of crucial importance.

Date: 2016
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DOI: 10.1038/ncomms10730

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