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

Author

Listed:
  • Nathan Harmston

    (MRC London Institute of Medical Sciences
    Imperial College London
    Duke-NUS Graduate Medical School)

  • Elizabeth Ing-Simmons

    (MRC London Institute of Medical Sciences
    Imperial College London
    Lymphocyte Development, MRC London Institute of Medical Sciences)

  • Ge Tan

    (MRC London Institute of Medical Sciences
    Imperial College London)

  • Malcolm Perry

    (MRC London Institute of Medical Sciences
    Imperial College London)

  • Matthias Merkenschlager

    (Imperial College London
    Lymphocyte Development, MRC London Institute of Medical Sciences)

  • Boris Lenhard

    (MRC London Institute of Medical Sciences
    Imperial College London
    University of Bergen)

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.

Suggested Citation

  • Nathan Harmston & Elizabeth Ing-Simmons & Ge Tan & Malcolm Perry & Matthias Merkenschlager & Boris Lenhard, 2017. "Topologically associating domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00524-5
    DOI: 10.1038/s41467-017-00524-5
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    Cited by:

    1. Varvara Lukyanchikova & Miroslav Nuriddinov & Polina Belokopytova & Alena Taskina & Jiangtao Liang & Maarten J. M. F. Reijnders & Livio Ruzzante & Romain Feron & Robert M. Waterhouse & Yang Wu & Chunh, 2022. "Anopheles mosquitoes reveal new principles of 3D genome organization in insects," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    2. David E. Torres & H. Martin Kramer & Vittorio Tracanna & Gabriel L. Fiorin & David E. Cook & Michael F. Seidl & Bart P. H. J. Thomma, 2024. "Implications of the three-dimensional chromatin organization for genome evolution in a fungal plant pathogen," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Thais Ealo & Victor Sanchez-Gaya & Patricia Respuela & María Muñoz-San Martín & Elva Martin-Batista & Endika Haro & Alvaro Rada-Iglesias, 2024. "Cooperative insulation of regulatory domains by CTCF-dependent physical insulation and promoter competition," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    4. Yi Liao & Juntao Wang & Zhangsheng Zhu & Yuanlong Liu & Jinfeng Chen & Yongfeng Zhou & Feng Liu & Jianjun Lei & Brandon S. Gaut & Bihao Cao & J. J. Emerson & Changming Chen, 2022. "The 3D architecture of the pepper genome and its relationship to function and evolution," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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