1. Active and Inactive Enhancers Cooperate to Exert Localized and Long-Range Control of Gene Regulation.
- Author
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Proudhon, Charlotte, Snetkova, Valentina, Raviram, Ramya, Lobry, Camille, Badri, Sana, Jiang, Tingting, Hao, Bingtao, Trimarchi, Thomas, Kluger, Yuval, Aifantis, Iannis, Bonneau, Richard, and Skok, Jane A
- Subjects
T-Lymphocytes ,Animals ,Mice ,Inbred C57BL ,Receptors ,Antigen ,T-Cell ,alpha-beta ,RNA ,Messenger ,Gene Rearrangement ,beta-Chain T-Cell Antigen Receptor ,Gene Expression Regulation ,Protein Binding ,Enhancer Elements ,Genetic ,Igk ,Tcrb ,enhancer-sharing ,gene regulation ,localized and long-range contacts ,nuclear architecture ,super-enhancer ,transcription factor binding ,transcriptional output ,Mice ,Inbred C57BL ,Receptors ,Antigen ,T-Cell ,alpha-beta ,RNA ,Messenger ,Gene Rearrangement ,beta-Chain T-Cell Antigen Receptor ,Enhancer Elements ,Genetic ,Biochemistry and Cell Biology ,Medical Physiology - 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.
- Published
- 2016