Inducible CTCF insulator delays the IgH 3′ regulatory region-mediated activation of germline promoters and alters class switching - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2017

Inducible CTCF insulator delays the IgH 3′ regulatory region-mediated activation of germline promoters and alters class switching

Fatima-Zohra Braikia
  • Fonction : Auteur
Chloé Oudinet
  • Fonction : Auteur
Dania Haddad
  • Fonction : Auteur
Zeliha Oruc
Domenico Orlando
  • Fonction : Auteur
Audrey Dauba
  • Fonction : Auteur
Ahmed Amine Khamlichi
  • Fonction : Auteur

Résumé

Class switch recombination (CSR) plays an important role in adaptive immune response by enabling mature B cells to switch from IgM expression to the expression of downstream isotypes. CSR is preceded by inducible germline (GL) transcription of the constant genes and is controlled by the 3′ regulatory region (3′RR) in a stimulus-dependent manner. Why the 3′RR-mediated up-regulation of GL transcription is delayed to the mature B-cell stage is presently unknown. Here we show that mice devoid of an inducible CTCF binding element, located in the α constant gene, display a marked isotype-specific increase of GL transcription in developing and resting splenic B cells and altered CSR in activated B cells. Moreover, insertion of a GL promoter downstream of the CTCF insulator led to premature activation of the ectopic promoter. This study provides functional evidence that the 3′RR has a developmentally controlled potential to constitutively activate GL promoters but that this activity is delayed, at least in part, by the CTCF insulator, which borders a transcriptionally active domain established by the 3′RR in developing B cells.

Dates et versions

hal-03477174 , version 1 (13-12-2021)

Identifiants

Citer

Fatima-Zohra Braikia, Chloé Oudinet, Dania Haddad, Zeliha Oruc, Domenico Orlando, et al.. Inducible CTCF insulator delays the IgH 3′ regulatory region-mediated activation of germline promoters and alters class switching. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114 (23), pp.6092-6097. ⟨10.1073/pnas.1701631114⟩. ⟨hal-03477174⟩
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