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

Harmston, Nathan, Ing-Simmons, Elizabeth, Tan, Ge, Perry, Malcolm, Merkenschlager, Matthias and Lenhard, Boris 2017. Topologically associated domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation. Nature Communications 8 , 441. 10.1101/042952

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Nature
Date of First Compliant Deposit:	23 August 2023
Date of Acceptance:	5 July 2017
Last Modified:	24 Aug 2023 19:38
URI:	https://orca.cardiff.ac.uk/id/eprint/161865

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