环挤压之外的增强子-启动子动态通讯
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1)香港科技大学(广州)功能枢纽先进材料学域,广州 511400;2)成都中医药大学医学技术学院,成都 611137

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国家自然科学基金(12474201),广东省珠江人才青年拔尖人才项目(2023QN10X037) 和广东省科技厅“1+1+1”联合资助计划 (2025A0505000027) 资助。


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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    摘要:

    增强子-启动子通讯是基因表达时空调控的基础。长期以来,黏连蛋白介导的环挤压被视为促进远端调控元件与靶启动子接近的重要结构机制。Aboreden等近期研究表明,在有丝分裂向G1期过渡过程中耗竭黏连蛋白加载与环挤压的关键调控因子NIPBL,会显著削弱结构性染色质环;然而,许多顺式调控接触及广泛的有丝分裂后转录再激活仅受到有限影响。该结果提示,环挤压是调控通讯的重要组成部分,但不足以单独解释增强子-启动子接触如何产生有效转录输出。本文探讨了转录凝聚体样组装如何作为额外的生化和动力学调控层,将调控元件之间的空间接近转化为功能性转录输出。通过在活跃基因位点附近局部富集转录因子、共激活因子、中介因子(mediator)和RNA聚合酶II,这类调控枢纽可能稳定有效的增强子-启动子相遇,并调节转录活性。基因表达输出可被分解为爆发频率、持续时间和大小等参数,基于此,转录爆发可为理解这一转化过程提供一个有用的动力学框架。因此,整合染色质结构、凝聚体组织与转录爆发动力学,有助于更全面地理解有丝分裂后增强子-启动子通讯如何重建,以及调控元件的空间接近如何通过环挤压之外的机制转化为转录输出。

    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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汤代延,楚夏昆.环挤压之外的增强子-启动子动态通讯[J].生物化学与生物物理进展,2026,53(9):2507-2512 TANG Dai-Yan, CHU Xia-Kun. Dynamic Enhancer–promoter Communication Beyond Loop Extrusion[J]. Progress in Biochemistry and Biophysics,2026,53(9):2507-2512

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  • 收稿日期:2026-05-14
  • 最后修改日期:2026-08-31
  • 录用日期:2026-07-14
  • 在线发布日期: 2026-07-15
  • 出版日期: 2026-09-28
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