Universität zu Köln

Vicioso-Mantis, Marta, Fueyo, Raquel, Navarro, Claudia, Cruz-Molina, Sara, van Ijcken, Wilfred F. J., Rebollo, Elena, Rada-Iglesias, Alvaro and Martinez-Balbas, Marian A. (2022). JMJD3 intrinsically disordered region links the 3D-genome structure to TGF beta-dependent transcription activation. Nat. Commun., 13 (1). BERLIN: NATURE PORTFOLIO. ISSN 2041-1723

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Abstract

Enhancers are key regulatory elements that govern gene expression programs in response to developmental signals. However, how multiple enhancers arrange in the 3D-space to control the activation of a specific promoter remains unclear. To address this question, we exploited our previously characterized TGF beta-response model, the neural stem cells, focusing on a similar to 374 kb locus where enhancers abound. Our 4C-seq experiments reveal that the TGF beta pathway drives the assembly of an enhancer-cluster and precise gene activation. We discover that the TGF beta pathway coactivator JMJD3 is essential to maintain these structures. Using live-cell imaging techniques, we demonstrate that an intrinsically disordered region contained in JMJD3 is involved in the formation of phase-separated biomolecular condensates, which are found in the enhancer-cluster. Overall, in this work we uncover novel functions for the coactivator JMJD3, and we shed light on the relationships between the 3D-conformation of the chromatin and the TGF beta-driven response during mammalian neurogenesis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vicioso-Mantis, Marta UNSPECIFIED UNSPECIFIED UNSPECIFIED Fueyo, Raquel UNSPECIFIED UNSPECIFIED UNSPECIFIED Navarro, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Cruz-Molina, Sara UNSPECIFIED UNSPECIFIED UNSPECIFIED van Ijcken, Wilfred F. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rebollo, Elena UNSPECIFIED UNSPECIFIED UNSPECIFIED Rada-Iglesias, Alvaro UNSPECIFIED UNSPECIFIED UNSPECIFIED Martinez-Balbas, Marian A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-685028
DOI:	10.1038/s41467-022-30614-y
Journal or Publication Title:	Nat. Commun.
Volume:	13
Number:	1
Date:	2022
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LIQUID-PHASE-SEPARATION; GROWTH-FACTOR-BETA; GENE-EXPRESSION; PROTEIN; ENHANCERS; RNA; DIFFERENTIATION; DETERMINANTS; INFLAMMATION; LANDSCAPES Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68502