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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.

Published Web Location

http://www.cell.com/cell-reports/fulltext/S2211-1247(16)30532-0
No data is associated with this publication.
Abstract

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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