Universität zu Köln

Crispatzu, Giuliano, Rehimi, Rizwan, Pachano, Tomas, Bleckwehl, Tore, Cruz-Molina, Sara, Xiao, Cally ORCID: 0000-0001-7172-3175, Mahabir, Esther, Bazzi, Hisham ORCID: 0000-0001-8388-4005 and Rada-Iglesias, Alvaro ORCID: 0000-0001-7137-1341 (2021). The chromatin, topological and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo. Nat. Commun., 12 (1). BERLIN: NATURE PORTFOLIO. ISSN 2041-1723

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Abstract

Poised enhancers (PEs) represent a genetically distinct set of distal regulatory elements that control the expression of major developmental genes. Before becoming activated in differentiating cells, PEs are already bookmarked in pluripotent cells with unique chromatin and topological features that could contribute to their privileged regulatory properties. However, since PEs were originally characterized in embryonic stem cells (ESC), it is currently unknown whether PEs are functionally conserved in vivo. Here, we show that the chromatin and 3D structural features of PEs are conserved among mouse pluripotent cells both in vitro and in vivo. We also uncovered that the interactions between PEs and their target genes are globally controlled by the combined action of Polycomb, Trithorax and architectural proteins. Moreover, distal regulatory sequences located close to developmental genes and displaying the typical genetic (i.e. CpG islands) and chromatin (i.e. high accessibility and H3K27me3 levels) features of PEs are commonly found across vertebrates. These putative PEs show high sequence conservation within specific vertebrate clades, with only a few being evolutionary conserved across all vertebrates. Lastly, by genetically disrupting PEs in mouse and chicken embryos, we demonstrate that these regulatory elements play essential roles during the induction of major developmental genes in vivo. Poised enhancers (PEs) in embryonic stem cells have accessible chromatin, are bound by repressive Polycomb Group proteins, and interact with their targets prior to activation. However, whether this is recapitulated in vivo is unknown. Here the authors show PEs display these features in mouse embryos, are prevalent across vertebrates, and are required for developmental gene expression.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Crispatzu, Giuliano UNSPECIFIED UNSPECIFIED UNSPECIFIED Rehimi, Rizwan UNSPECIFIED UNSPECIFIED UNSPECIFIED Pachano, Tomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Bleckwehl, Tore UNSPECIFIED UNSPECIFIED UNSPECIFIED Cruz-Molina, Sara UNSPECIFIED UNSPECIFIED UNSPECIFIED Xiao, Cally UNSPECIFIED orcid.org/0000-0001-7172-3175 UNSPECIFIED Mahabir, Esther UNSPECIFIED UNSPECIFIED UNSPECIFIED Bazzi, Hisham UNSPECIFIED orcid.org/0000-0001-8388-4005 UNSPECIFIED Rada-Iglesias, Alvaro UNSPECIFIED orcid.org/0000-0001-7137-1341 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-591564
DOI:	10.1038/s41467-021-24641-4
Journal or Publication Title:	Nat. Commun.
Volume:	12
Number:	1
Date:	2021
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROMOTER INTERACTIONS; GENOME ARCHITECTURE; H2A UBIQUITYLATION; READ ALIGNMENT; PRC1 COMPLEX; CPG ISLANDS; DNA LOOPS; POLYCOMB; DOMAINS; METHYLATION Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59156