کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2039194 | 1073034 | 2016 | 11 صفحه PDF | دانلود رایگان |
• Synergistic contacts between the elements of a super-enhancer contribute to activity
• Igk enhancers play diverse roles in lymphocyte development
• The Igk enhancer, MiEκ, contributes to regulation of Tcrb recombination
• Enhancer sharing can involve active as well as inactive regulatory elements
SummaryV(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.
Graphical AbstractFigure optionsDownload as PowerPoint slide
Journal: - Volume 15, Issue 10, 7 June 2016, Pages 2159–2169