title: Elucidation of IgH 3' region regulatory role during class switch recombination via germline deletion.
abstract: In mature B cells, class switch recombination (CSR) replaces the expressed constant Cμ gene with a downstream C(H) gene. How the four transcriptional enhancers of the IgH 3' regulatory region (3'RR) control CSR remains an open question. We have investigated IgG1 CSR in 3'RR-deficient mice. Here we show that the 3'RR enhancers target the S(γ1) acceptor region (and poorly the S(μ) donor region) by acting on epigenetic marks, germline transcription, paused RNA Pol II recruitment, R loop formation, AID targeting and double-strand break generation. In contrast, location and diversity of S(μ)-S(γ1) junctions are not affected by deletion of the 3'RR enhancers. Thus, the 3'RR controls the first steps of CSR by priming the S acceptor region but is not implicated in the choice of the end-joining pathway.
authors.affiliation: 1] Université de Limoges, CRIBL, UMR 7276, Limoges 87000, France [2] CNRS UMR 7276, Limoges 87000, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Saintamand
authors.affiliation: 1] Université de Limoges, CRIBL, UMR 7276, Limoges 87000, France [2] CNRS UMR 7276, Limoges 87000, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Rouaud
authors.affiliation: 1] Université de Limoges, CRIBL, UMR 7276, Limoges 87000, France [2] CNRS UMR 7276, Limoges 87000, France.
authors.forename: Faten
authors.initials: F
authors.lastname: Saad
authors.affiliation: CNRS et Université de Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 6097, Sophia Antipolis 06560, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Rios
authors.affiliation: 1] Université de Limoges, CRIBL, UMR 7276, Limoges 87000, France [2] CNRS UMR 7276, Limoges 87000, France [3] Institut Universitaire de France, Paris 87025, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Cogné
authors.affiliation: 1] Université de Limoges, CRIBL, UMR 7276, Limoges 87000, France [2] CNRS UMR 7276, Limoges 87000, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Denizot
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D044127:Epigenesis, Genetic; D005260:Female; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007134:Immunoglobulin Switch Region; D008297:Male; D051379:Mice; D011994:Recombinant Proteins; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000166:cytology*
chemical_list: D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D011994:Recombinant Proteins