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Open Access Publications from the University of California

Active and Inactive Enhancers Cooperate to Exert Localized and Long-Range Control of Gene Regulation.

  • Author(s): Proudhon, Charlotte;
  • Snetkova, Valentina;
  • Raviram, Ramya;
  • Lobry, Camille;
  • Badri, Sana;
  • Jiang, Tingting;
  • Hao, Bingtao;
  • Trimarchi, Thomas;
  • Kluger, Yuval;
  • Aifantis, Iannis;
  • Bonneau, Richard;
  • Skok, Jane A
  • et al.

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V(D)J recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR) loci in a lineage- and stage-specific manner. Unexpectedly, we find that both active and inactive AgR enhancers cooperate to disseminate their effects in a localized and long-range manner. Here, we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. Furthermore, we establish that, in T cells, long-range contact and cooperation between the inactive Igk enhancer MiEκ and the active Tcrb enhancer Eβ alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage- and stage-specific control.

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