RNA-Binding Proteins Mediate the Maturation of Chromatin Topology During Differentiation

Authors

Bondita Dehingia
Małgorzata Milewska-Puchała
Marcin Janowski
Mahmoud-Reza Rafiee
Misbah Abbas
Aleksandra Piotrowska
Jan Senge
Piotr Blaut
Dietrich Walsh
Jacqueline Severino
Debadeep Chaudhury
Sajjad Iqbal
Rogelio Montiel-Manriquez
Sylwia Jankowska
Peyman Zare
Wolfgang Huber
Jianliang Xu
Rafael Casellas
Timo Zimmermann
Paweł Dłotko
Jeroen Krijgsveld
Aleksandra Pękowska

Language

English

Publication Date

9-1-2025

Journal

Nature Cell Biology

DOI

10.1038/s41556-025-01735-5

PMID

40921733

PMCID

PMC12431861

PubMedCentral® Posted Date

9-8-2025

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Animals, CCCTC-Binding Factor, Chromatin, Cell Differentiation, Neural Stem Cells, Mice, Mouse Embryonic Stem Cells, RNA-Binding Proteins, Gene Expression Regulation, Developmental, Chromatin Assembly and Disassembly, Protein Binding, Embryonic Stem Cells, Neurogenesis

Published Open-Access

yes

Recommended Citation

Dehingia, Bondita; Milewska-Puchała, Małgorzata; Janowski, Marcin; et al., "RNA-Binding Proteins Mediate the Maturation of Chromatin Topology During Differentiation" (2025). Faculty, Staff and Student Publications. 5447.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5447