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Nat Commun. 2017 Sep 5;8(1):441. doi: 10.1038/s41467-017-00524-5.

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

Author information

1
Computational Regulatory Genomics, MRC London Institute of Medical Sciences, London, W12 0NN, UK. nathan.harmston@duke-nus.edu.sg.
2
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, W12 0NN, UK. nathan.harmston@duke-nus.edu.sg.
3
Program in Cardiovascular and Metabolic Disease, Duke-NUS Graduate Medical School, 8 College Road, Singapore, 169857, Singapore. nathan.harmston@duke-nus.edu.sg.
4
Computational Regulatory Genomics, MRC London Institute of Medical Sciences, London, W12 0NN, UK.
5
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, W12 0NN, UK.
6
Lymphocyte Development, MRC London Institute of Medical Sciences, London, W12 0NN, UK.
7
Computational Regulatory Genomics, MRC London Institute of Medical Sciences, London, W12 0NN, UK. b.lenhard@imperial.ac.uk.
8
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, W12 0NN, UK. b.lenhard@imperial.ac.uk.
9
Sars International Centre for Marine Molecular Biology, University of Bergen, N-5008, Bergen, Norway. b.lenhard@imperial.ac.uk.

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.

PMID:
28874668
PMCID:
PMC5585340
DOI:
10.1038/s41467-017-00524-5
[Indexed for MEDLINE]
Free PMC Article

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