Dynamic Enhancer–promoter Communication Beyond Loop Extrusion
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1)Advanced Materials Thrust, Function Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou 511400, China;2)School of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China

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This work was supported by grants from The National Natural Science Foundation of China (12474201), the Guangdong Pearl River Talent Program for Young Top Talents (2023QN10X037), and the Guangdong Provincial Department of Science and Technology “1+1+1” Joint Funding Program (2025A0505000027).

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    Abstract:

    Enhancer-promoter communication is fundamental to the spatial and temporal control of gene expression. Cohesin-mediated loop extrusion has long been considered a major structural mechanism that brings distal regulatory elements into proximity with their target promoters. Recent findings from Aboreden et al. refine this view by showing that depletion of Nipped-B-like protein (NIPBL), a key regulator of cohesin loading and loop extrusion, markedly disrupts architectural chromatin loops, whereas many cis-regulatory contacts and broad post-mitotic transcriptional reactivation are only modestly affected. These observations suggest that loop extrusion is important, but not sufficient, for explaining productive regulatory communication. In this Comment, we discuss how transcriptional condensate-like assemblies may provide an additional biochemical and kinetic layer that helps convert regulatory proximity into transcriptional output. By locally enriching transcription factors, coactivators, Mediator and RNA polymerase II (Pol II) around active loci, such regulatory hubs may stabilize productive enhancer–promoter encounters and modulate transcriptional activity. We further propose that transcriptional bursting provides a useful framework for understanding this conversion, because gene expression can be decomposed into burst frequency, burst duration and burst size. Integrating chromatin architecture, condensate organization and bursting dynamics may therefore provide a more complete view of how enhancer-promoter communication is re-established after mitosis and how regulatory proximity is converted into transcriptional output through mechanisms beyond loop extrusion.

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TANG Dai-Yan, CHU Xia-Kun. Dynamic Enhancer–promoter Communication Beyond Loop Extrusion[J]. Progress in Biochemistry and Biophysics,,():

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History
  • Received:May 14,2026
  • Revised:July 14,2026
  • Adopted:July 14,2026
  • Online: July 15,2026
  • Published:
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