title: Deciphering the importance of the palindromic architecture of the immunoglobulin heavy-chain 3' regulatory region.
abstract: The IgH 3' regulatory region (3'RR) controls class switch recombination (CSR) and somatic hypermutation (SHM) in B cells. The mouse 3'RR contains four enhancer elements with hs1,2 flanked by inverted repeated sequences and the centre of a 25-kb palindrome bounded by two hs3 enhancer inverted copies (hs3a and hs3b). hs4 lies downstream of the palindrome. In mammals, evolution maintained this unique palindromic arrangement, suggesting that it is functionally significant. Here we report that deconstructing the palindromic IgH 3'RR strongly affects its function even when enhancers are preserved. CSR and IgH transcription appear to be poorly dependent on the 3'RR architecture and it is more or less preserved, provided 3'RR enhancers are present. By contrast, a 'palindromic effect' significantly lowers VH germline transcription, AID recruitment and SHM. In conclusion, this work indicates that the IgH 3'RR does not simply pile up enhancer units but also optimally exposes them into a functional architecture of crucial importance.
authors.affiliation: Université de Limoges, CRIBL, UMR CNRS 7276, Limoges 87025, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Saintamand
authors.affiliation: Université de Limoges, CRIBL, UMR CNRS 7276, Limoges 87025, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Vincent-Fabert
authors.affiliation: Université de Limoges, CRIBL, UMR CNRS 7276, Limoges 87025, France.
authors.forename: Armand
authors.initials: A
authors.lastname: Garot
authors.affiliation: Université de Limoges, CRIBL, UMR CNRS 7276, Limoges 87025, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Rouaud
authors.affiliation: Université de Limoges, CRIBL, UMR CNRS 7276, Limoges 87025, France.
authors.forename: Zeliha
authors.initials: Z
authors.lastname: Oruc
authors.affiliation: CNRS et Université de Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 6097, Sophia Antipolis 06560, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Magnone
authors.affiliation: Université de Limoges, CRIBL, UMR CNRS 7276, Limoges 87025, France.|Institut Universitaire de France, Paris 75231, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Cogné
authors.affiliation: Université de Limoges, CRIBL, UMR CNRS 7276, Limoges 87025, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Denizot
mesh_terms: D000818:Animals; D005260:Female; D017578:Immunoglobulin Class Switching; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D055029:Inverted Repeat Sequences; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D007143:Immunoglobulin Heavy Chains