Journal Article

DKFZ-2025-03051

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Two distinct chromatin modules regulate proinflammatory gene expression.

Seufert, I. (First author)DKFZ* ; Gerosa, I.DKFZ* ; Varamogianni-Mamatsi, V. ; Vladimirova, A.DKFZ* ; Sen, E.DKFZ* ; Mantz, S.DKFZ* ; Rademacher, A.DKFZ* ; Schumacher, S.DKFZ* ; Liakopoulos, P. ; Kolovos, P. ; Anders, S. ; Mallm, J.-P.DKFZ* ; Papantonis, A. ; Rippe, K. (Last author)DKFZ*

2026
Nature America New York, NY

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.

Note: #EA:B066#LA:B066# / 2026 Jan;28(1):182-196

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Contributing Institute(s):

1. B066 Chromatin-Netzwerke (B066)
2. Single-cell Open Lab (W192)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 20 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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