title: The IgH locus 3' cis-regulatory super-enhancer co-opts AID for allelic transvection.
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.
authors.affiliation: UMR 7276 CNRS and Université de Limoges: Contrôle de la Réponse Immune B et Lymphoprolifération, Limoges, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Le Noir
authors.affiliation: UMR 7276 CNRS and Université de Limoges: Contrôle de la Réponse Immune B et Lymphoprolifération, Limoges, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Laffleur
authors.affiliation: UMR 7276 CNRS and Université de Limoges: Contrôle de la Réponse Immune B et Lymphoprolifération, Limoges, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Carrion
authors.affiliation: UMR 7276 CNRS and Université de Limoges: Contrôle de la Réponse Immune B et Lymphoprolifération, Limoges, France.
authors.forename: Armand
authors.initials: A
authors.lastname: Garot
authors.affiliation: UMR 7276 CNRS and Université de Limoges: Contrôle de la Réponse Immune B et Lymphoprolifération, Limoges, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lecardeur
authors.affiliation: UMR 7276 CNRS and Université de Limoges: Contrôle de la Réponse Immune B et Lymphoprolifération, Limoges, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Pinaud
authors.affiliation: UMR 7276 CNRS and Université de Limoges: Contrôle de la Réponse Immune B et Lymphoprolifération, Limoges, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Denizot
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Skok
authors.affiliation: UMR 7276 CNRS and Université de Limoges: Contrôle de la Réponse Immune B et Lymphoprolifération, Limoges, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Cogné
mesh_terms: D024509:3' Flanking Region / Q000235:genetics; D000483:Alleles; D000818:Animals; D002469:Cell Separation; D003564:Cytidine Deaminase / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D007143:Immunoglobulin Heavy Chains; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: alleles; gene regulation; nuclear positioning; super-enhancer; transvection