Research Papers:
The IgH locus 3’ cisregulatory superenhancer coopts AID for allelic transvection
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Sandrine Le Noir1,*, Brice Laffleur1,*, Claire Carrion1, Armand Garot1, Sandrine Lecardeur1, Eric Pinaud1, Yves Denizot1, Jane Skok2 and Michel Cogné1
1 UMR 7276 CNRS and Université de Limoges: Contrôle de la Réponse Immune B et Lymphoprolifération, Limoges, France
2 Department of Pathology, New York University School of Medicine, New York, NY, USA
* These authors have contributed equally to this work
Correspondence to:
Michel Cogné, email:
Keywords: super-enhancer; alleles; transvection; nuclear positioning; gene regulation
Received: December 20, 2016 Accepted: January 01, 2017 Published: February 21, 2017
Abstract
Immunoglobulin heavy chain (IgH) alleles have ambivalent relationships: they feature both allelic exclusion, ensuring monoallelic expression of a single immunoglobulin (Ig) allele, and frequent inter-allelic class-switch recombination (CSR) reassembling genes from both alleles. The IgH locus 3’ regulatory region (3’RR) includes several transcriptional cis-enhancers promoting activation-induced cytidine deaminase (AID)-dependent somatic hypermutation (SHM) and CSR, and altogether behaves as a strong super-enhancer. It can also promote deregulated expression of translocated oncogenes during lymphomagenesis. Besides these rare, illegitimate and pathogenic interactions, we now show that under physiological conditions, the 3’RR super-enhancer supports not only legitimate cis- , but also trans-recruitment of AID, contributing to IgH inter-allelic proximity and enabling the super-enhancer on one allele to stimulate biallelic SHM and CSR. Such inter-allelic activating interactions define transvection, a phenomenon well-known in drosophila but rarely observed in mammalian cells, now appearing as a unique feature of the IgH 3’RR super-enhancer.