The IgH locus 3' cis-regulatory super-enhancer co-opts AID for allelic transvection.

The IgH locus 3' cis-regulatory super-enhancer co-opts AID for allelic transvection.

Oncotarget. 2017 Jan 10;:

Authors: Le Noir S, Laffleur B, Carrion C, Garot A, Lecardeur S, Pinaud E, Denizot Y, Skok J, Cogné M

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.

PMID: 28088785 [PubMed - as supplied by publisher]

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