海德堡大学Karsten Rippe课题组宣布他们的最新研究探明了两种不同的染色质模块调节促炎基因的表达。2025年12月24日出版的《自然—细胞生物学》杂志发表了这项成果。

在这里，该团队解剖由肿瘤坏死因子（TNF）诱导的促炎基因表达程序在人内皮细胞主题测序和成像为基础的方法。他们的发现，通过使用RWireX软件对深度覆盖的单细胞染色质可及性数据进行共可及性分析，确定了两种不同的调节染色质模块：分离位点之间的共可及性（ACs）的自主链接和增加局部转录因子结合的连续共可及性（DCs）结构域。AC和DC模块中基因的TNF依赖性诱导时间和强度以及转录破裂动力学的变化不同，表明功能上不同的调控机制。这些发现为理解细胞如何实现基因表达的快速和精确控制提供了一个框架。

据了解，基因激活和协同调节被归因于不同的机制，如通过染色质环增强子-启动子相互作用或转录因子积聚成枢纽或凝聚体。然而，探索人类原代细胞内源性基因调控机制差异的全基因组研究很少。

附：英文原文

Title: Two distinct chromatin modules regulate proinflammatory gene expression

Author: Seufert, Isabelle, Gerosa, Irene, Varamogianni-Mamatsi, Vassiliki, Vladimirova, Anastasiya, Sen, Ezgi, Mantz, Stefanie, Rademacher, Anne, Schumacher, Sabrina, Liakopoulos, Panagiotis, Kolovos, Petros, Anders, Simon, Mallm, Jan-Philipp, Papantonis, Argyris, Rippe, Karsten

Issue&Volume: 2025-12-24

Abstract: Gene activation and coregulation have been attributed to different mechanisms, such as enhancer–promoter interactions via chromatin looping or the accumulation of transcription factors into hubs or condensates. However, genome-wide studies exploring mechanistic differences in endogenous gene regulation in primary human cells are scarce. Here we dissect the proinflammatory gene expression programme induced by tumor necrosis factor (TNF) in human endothelial cells using sequencing- and imaging-based methods. Our findings, enabled by the co-accessibility analysis of deep-coverage single-cell chromatin accessibility data with our RWireX software, identified two distinct regulatory chromatin modules: autonomous links of co-accessibility (ACs) between separated sites and domains of contiguous co-accessibility (DCs) with increased local transcription factor binding. The TNF-dependent induction timing and strength as well as changes in transcriptional bursting kinetics differed for genes in the AC and DC modules, pointing to functionally distinct regulatory mechanisms. These findings provide a framework for understanding how cells achieve rapid and precise control of gene expression.

DOI: 10.1038/s41556-025-01819-2

Source: https://www.nature.com/articles/s41556-025-01819-2