title: Functional anatomy of the immunoglobulin heavy chain 3΄ super-enhancer needs not only core enhancer elements but also their unique DNA context.
abstract: Cis-regulatory elements feature clustered sites for transcription factors, defining core enhancers and have inter-species homology. The mouse IgH 3΄ regulatory region (3'RR), a major B-cell super-enhancer, consists of four of such core enhancers, scattered throughout more than 25 kb of packaging 'junk DNA', the sequence of which is not conserved but follows a unique palindromic architecture which is conserved in all mammalian species. The 3'RR promotes long-range interactions and potential IgH loops with upstream promoters, controlling class switch recombination (CSR) and somatic hypermutation (SHM). It was thus of interest to determine whether this functional architecture also involves the specific functional structure of the super-enhancer itself, potentially promoted by its symmetric DNA shell. Since many transgenic 3'RR models simply linked core enhancers without this shell, it was also important to compare such a 'core 3'RR' (c3'RR) with the intact full-length super-enhancer in an actual endogenous IgH context. Packaging DNA between 3'RR core enhancers proved in fact to be necessary for optimal SHM, CSR and IgH locus expression in plasma cells. This reveals that packaging DNA can matter in the functional anatomy of a super-enhancer, and that precise evaluation of such elements requires full consideration of their global architecture.
authors.affiliation: UMR 7276 CNRS and Université de Limoges: Contrôle de la Réponse Immune B et Lymphoprolifération, 2 rue du Dr. Descottes, 87025 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, 2 rue du Dr. Descottes, 87025 Limoges, France.
authors.forename: François
authors.initials: F
authors.lastname: Boyer
authors.affiliation: UMR 7276 CNRS and Université de Limoges: Contrôle de la Réponse Immune B et Lymphoprolifération, 2 rue du Dr. Descottes, 87025 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, 2 rue du Dr. Descottes, 87025 Limoges, France.
authors.forename: Mylène
authors.initials: M
authors.lastname: Brousse
authors.affiliation: UMR 7276 CNRS and Université de Limoges: Contrôle de la Réponse Immune B et Lymphoprolifération, 2 rue du Dr. Descottes, 87025 Limoges, France.
authors.forename: Zeliha
authors.initials: Z
authors.lastname: Oruc
authors.affiliation: UMR 7276 CNRS and Université de Limoges: Contrôle de la Réponse Immune B et Lymphoprolifération, 2 rue du Dr. Descottes, 87025 Limoges, France.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Cook-Moreau
authors.affiliation: UMR 7276 CNRS and Université de Limoges: Contrôle de la Réponse Immune B et Lymphoprolifération, 2 rue du Dr. Descottes, 87025 Limoges, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Denizot
authors.affiliation: UMR 7276 CNRS and Université de Limoges: Contrôle de la Réponse Immune B et Lymphoprolifération, 2 rue du Dr. Descottes, 87025 Limoges, France.|Institut Universitaire de France, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Cogné
mesh_terms: D020413:3' Untranslated Regions / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D004247:DNA / Q000235:genetics / Q000276:immunology; D004742:Enhancer Elements, Genetic / Q000276:immunology*; D056426:Genetic Loci; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000145:classification / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000276:immunology*; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D007143:Immunoglobulin Heavy Chains; D004247:DNA