中山大学丁俊军小组的一项最新研究探明了JMJD2通过生物分子凝聚形成调节增强子-启动子相互作用。相关论文于2025年12月16日发表在《自然—遗传学》杂志上。

在这里，课题组研究人员提出了一种基于染色质相互作用的蛋白质组学方法，LoopID，来分析某些E-P锚点上的蛋白质（称为环体）。该课题组人员发现组蛋白去甲基酶JMJD2是环体的关键成分，它可以通过形成生物分子凝聚物以不依赖催化的方式调节E-P相互作用和环体。

此外，研究组引入了一个系统，通过在某些基因组位点组装JMJD2凝聚物来设计E-P相互作用，从而构建细胞类型特异性的E-P相互作用，从而促进细胞重编程为多能或双细胞样细胞。他们的发现揭示了组蛋白去甲基化酶在调节染色质组织中的非规范功能，并提供了一种通过E-P相互作用调节细胞命运转变的策略。

据悉，增强子-启动子（E-P）相互作用调节细胞命运决定过程中的转录。然而，E-P相互作用的调控机制仍然是未知的。

附：英文原文

Title: JMJD2 regulates enhancer–promoter interactions via biomolecular condensate formation

Author: Jiang, Shaoshuai, Liu, Xinyi, Zhang, Zhuheng, Yang, Mingzhu, Zhu, Xing, Ma, Lin, Zhao, Longying, Ling, Xiaoru, Zhou, Ziqiang, Wu, Ziqiang, Qu, Jiale, Li, Haochen, Liang, Jiawei, Deng, Zhiheng, Tian, Qi, Huang, Xiaona, Huang, Xianglin, Tan, Jin, Sun, Jun, Wang, Jia, Guallar, Diana, Das, Partha Pratim, Pinello, Luca, Wang, Liang, Wu, Hongfu, Huang, Dong-feng, Wang, Jichang, Lin, Hancheng, Bai, Jin, Fan, Lili, Chi, Wei, Xiao, Xue, Ding, Junjun

Issue&Volume: 2025-12-16

Abstract: Enhancer–promoter (E-P) interactions regulate transcription during cell fate determination. However, the regulatory mechanisms underlying E-P interactions have remained elusive. Here we present a chromatin-interaction-based proteomic approach, LoopID, to profile proteins (termed the looposome) at certain E-P anchors. We find that histone demethylase JMJD2, a key looposome component, can regulate E-P interactions and the looposome in a catalytic-independent manner through formation of biomolecular condensates. Furthermore, we introduce a system to engineer E-P interactions by assembling JMJD2 condensates at certain genomic loci, enabling construction of cell-type-specific E-P interactions to promote cellular reprogramming into pluripotent or two-cell-like cells. Our findings reveal a noncanonical function of a histone demethylase in regulation of chromatin organization and provide a strategy to regulate cell fate transitions through E-P interactions.

DOI: 10.1038/s41588-025-02415-8

Source: https://www.nature.com/articles/s41588-025-02415-8