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Topologically associating domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation.

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Title: Topologically associating domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation.
Authors: Harmston, N
Ing-Simmons, E
Tan, G
Perry, M
Merkenschlager, M
Lenhard, B
Item Type: Journal Article
Abstract: Developmental genes in metazoan genomes are surrounded by dense clusters of conserved noncoding elements (CNEs). CNEs exhibit unexplained extreme levels of sequence conservation, with many acting as developmental long-range enhancers. Clusters of CNEs define the span of regulatory inputs for many important developmental regulators and have been described previously as genomic regulatory blocks (GRBs). Their function and distribution around important regulatory genes raises the question of how they relate to 3D conformation of these loci. Here, we show that clusters of CNEs strongly coincide with topological organisation, predicting the boundaries of hundreds of topologically associating domains (TADs) in human and Drosophila. The set of TADs that are associated with high levels of noncoding conservation exhibit distinct properties compared to TADs devoid of extreme noncoding conservation. The close correspondence between extreme noncoding conservation and TADs suggests that these TADs are ancient, revealing a regulatory architecture conserved over hundreds of millions of years.Metazoan genomes contain many clusters of conserved noncoding elements. Here, the authors provide evidence that these clusters coincide with distinct topologically associating domains in humans and Drosophila, revealing a conserved regulatory genomic architecture.
Issue Date: 5-Sep-2017
Date of Acceptance: 5-Jul-2017
URI: http://hdl.handle.net/10044/1/50525
DOI: https://dx.doi.org/10.1038/s41467-017-00524-5
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 8
Issue: 1
Copyright Statement: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. © The Author(s) 2017
Keywords: MD Multidisciplinary
Publication Status: Published online
Conference Place: England
Article Number: 441
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



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