Journal Article

DKFZ-2025-01878

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png RNA-binding proteins mediate the maturation of chromatin topology during differentiation.

Dehingia, B. ; Milewska-Puchała, M. ; Janowski, M. ; Rafiee, M.-R. ; Abbas, M. ; Piotrowska, A. ; Senge, J. ; Blaut, P. ; Walsh, D. ; Severino, J. ; Chaudhury, D. ; Iqbal, S. ; Montiel-Manriquez, R. ; Jankowska, S. ; Zare, P. ; Huber, W. ; Xu, J. ; Casellas, R. ; Zimmermann, T. ; Dłotko, P. ; Krijgsveld, J.DKFZ* ; Pękowska, A.

2025
Nature America New York, NY

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Please use a persistent id in citations: doi:10.1038/s41556-025-01735-5

Abstract: Topologically associating domains (TADs) and chromatin architectural loops impact promoter-enhancer interactions, with CCCTC-binding factor (CTCF) defining TAD borders and loop anchors. TAD boundaries and loops progressively strengthen upon embryonic stem (ES) cell differentiation, underscoring the importance of chromatin topology in ontogeny. However, the mechanisms driving this process remain unclear. Here we show a widespread increase in CTCF-RNA-binding protein (RBP) interactions upon ES to neural stem (NS) cell differentiation. While dispensable in ES cells, RBPs reinforce CTCF-anchored chromatin topology in NS cells. We identify Pantr1, a non-coding RNA, as a key facilitator of CTCF-RBP interactions, promoting chromatin maturation. Using acute CTCF degradation, we find that, through its insulator function, CTCF helps maintain neuronal gene silencing in NS cells by acting as a barrier to untimely gene activation during development. Altogether, we reveal a fundamental mechanism driving developmentally linked chromatin structural consolidation and the contribution of this process to the control of gene expression in differentiation.

Note: 2025 Sep;27(9):1510-1525

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Contributing Institute(s):

1. B230 Proteomik von Stammzellen und Krebs (B230)

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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