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Two distinct chromatin modules regulate proinflammatory gene expression

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 regulat...

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Main Authors: Seufert, Isabelle (Author) , Gerosa, Irene (Author) , Varamogianni-Mamatsi, Vassiliki (Author) , Vladimirova, Anastasiya (Author) , Sen, Ezgi (Author) , Mantz, Stefanie (Author) , Rademacher, Anne (Author) , Schumacher, Sabrina (Author) , Liakopoulos, Panagiotis (Author) , Kolovos, Petros (Author) , Anders, Simon (Author) , Mallm, Jan-Philipp (Author) , Papantonis, Argyris (Author) , Rippe, Karsten (Author)
Format: Article (Journal)
Language:English
Published: 24 December 2025
In: Nature cell biology
Year: 2026, Volume: 28, Issue: 1, Pages: 182-196
ISSN:1476-4679
DOI:10.1038/s41556-025-01819-2
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41556-025-01819-2
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41556-025-01819-2
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Author Notes:Isabelle Seufert, Irene Gerosa, Vassiliki Varamogianni-Mamatsi, Anastasiya Vladimirova, Ezgi Sen, Stefanie Mantz, Anne Rademacher, Sabrina Schumacher, Panagiotis Liakopoulos, Petros Kolovos, Simon Anders, Jan-Philipp Mallm, Argyris Papantonis and Karsten Rippe
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Summary: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.
Item Description:Gesehen am 24.03.2026
Physical Description:Online Resource
ISSN:1476-4679
DOI:10.1038/s41556-025-01819-2

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