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

Fatima Zohra Braikia, Chloé Oudinet, Dania Haddad, Zeliha Oruc, Domenico Orlando, Audrey Dauba, Marc L. Le Bert, Ahmed Amine Khamlichi

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

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 upregulation 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 a 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.

Original languageEnglish
Pages (from-to)6092-6097
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number23
DOIs
Publication statusPublished - 6 Jun 2017

Keywords

  • B lymphocyte
  • Class switch recombination
  • Germline transcription
  • IgH locus
  • Insulator

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