title: Enhancers located in heavy chain regulatory region (hs3a, hs1,2, hs3b, and hs4) are dispensable for diversity of VDJ recombination.
abstract: V(D)J recombination occurs during the antigen-independent early steps of B-cell ontogeny. Multiple IgH cis-regulatory elements control B-cell ontogeny. IGCR1 (intergenic control region 1), the DQ52 promoter/enhancer, and the intronic Emu enhancer, all three located upstream of Cmu, have important roles during V(D)J recombination, whereas there is no clue about a role of the IgH regulatory region (RR) encompassing the four transcriptional enhancers hs3a, hs1,2, hs3b, and hs4 during these early stages. To clarify the role of the RR in V(D)J recombination, we totally deleted it in the mouse genome. Here, we show that V(D)J recombination is unaffected by the complete absence of the IgH RR, highlighting that this region only orchestrates IgH locus activity during the late stages of B-cell differentiation. In contrast, the earliest antigen-independent steps of B-cell ontogeny would be under the control of only the upstream Cmu elements of the locus.
authors.affiliation: UMR CNRS 7276, Centre National de la Recherche Scientifique, Université de Limoges, 87025 Limoges Cedex, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Rouaud
authors.forename: Christelle
authors.initials: C
authors.lastname: Vincent-Fabert
authors.forename: Remi
authors.initials: R
authors.lastname: Fiancette
authors.forename: Michel
authors.initials: M
authors.lastname: Cogné
authors.forename: Eric
authors.initials: E
authors.lastname: Pinaud
authors.forename: Yves
authors.initials: Y
authors.lastname: Denizot
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D056426:Genetic Loci / Q000502:physiology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D060152:V(D)J Recombination / Q000502:physiology*
chemical_list: D007143:Immunoglobulin Heavy Chains