Universität zu Köln

Cruz-Molina, Sara, Respuela, Patricia ORCID: 0000-0002-9719-7860, Tebartz, Christina, Kolovos, Petros ORCID: 0000-0002-0787-6158, Nikolic, Milos ORCID: 0000-0003-0029-7601, Fueyo, Raquel, van Ijcken, Wilfred F. J., Grosveld, Frank, Frommolt, Peter ORCID: 0000-0002-1966-8014, Bazzi, Hisham ORCID: 0000-0001-8388-4005 and Rada-Iglesias, Alvaro (2017). PRC2 Facilitates the Regulatory Topology Required for Poised Enhancer Function during Pluripotent Stem Cell Differentiation. Cell Stem Cell, 20 (5). S. 689 - 715. CAMBRIDGE: CELL PRESS. ISSN 1875-9777

Full text not available from this repository.

Abstract

Poised enhancers marked by H3K27me3 in pluripotent stem cells have been implicated in the establishment of somatic expression programs during embryonic stem cell (ESC) differentiation. However, the functional relevance and mechanism of action of poised enhancers remain unknown. Using CRISPR/Cas9 technology to engineer precise genetic deletions, we demonstrate that poised enhancers are necessary for the induction of major anterior neural regulators. Interestingly, circularized chromosome conformation capture sequencing (4C-seq) shows that poised enhancers already establish physical interactions with their target genes in ESCs in a polycomb repressive complex 2 (PRC2)-dependent manner. Loss of PRC2 does not activate poised enhancers or induce their putative target genes in undifferentiated ESCs; however, loss of PRC2 in differentiating ESCs severely and specifically compromises the induction of major anterior neural genes representing poised enhancer targets. Overall, our work illuminates an unexpected function for polycomb proteins in facilitating neural induction by endowing major anterior neural loci with a permissive regulatory topology.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Cruz-Molina, Sara UNSPECIFIED UNSPECIFIED UNSPECIFIED Respuela, Patricia UNSPECIFIED orcid.org/0000-0002-9719-7860 UNSPECIFIED Tebartz, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Kolovos, Petros UNSPECIFIED orcid.org/0000-0002-0787-6158 UNSPECIFIED Nikolic, Milos UNSPECIFIED orcid.org/0000-0003-0029-7601 UNSPECIFIED Fueyo, Raquel UNSPECIFIED UNSPECIFIED UNSPECIFIED van Ijcken, Wilfred F. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Grosveld, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Frommolt, Peter UNSPECIFIED orcid.org/0000-0002-1966-8014 UNSPECIFIED Bazzi, Hisham UNSPECIFIED orcid.org/0000-0001-8388-4005 UNSPECIFIED Rada-Iglesias, Alvaro UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-231330
DOI:	10.1016/j.stem.2017.02.004
Journal or Publication Title:	Cell Stem Cell
Volume:	20
Number:	5
Page Range:	S. 689 - 715
Date:	2017
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1875-9777
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHROMOSOME CONFORMATION CAPTURE; REPRESSIVE COMPLEX 2; TRANSCRIPTION FACTORS; GENE-EXPRESSION; GENOME-WIDE; POLYCOMB; RECRUITMENT; ALIGNMENT; ELEMENTS; PLATFORM Multiple languages Cell & Tissue Engineering; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23133