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Stratification of TAD boundaries reveals preferential insulation of super-enhancers by strong boundaries

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Listed:
  • Yixiao Gong

    (NYU School of Medicine
    NYU School of Medicine)

  • Charalampos Lazaris

    (NYU School of Medicine
    NYU School of Medicine)

  • Theodore Sakellaropoulos

    (National Technical University of Athens)

  • Aurelie Lozano

    (IBM T.J. Watson Research Center)

  • Prabhanjan Kambadur

    (Bloomberg LP)

  • Panagiotis Ntziachristos

    (Northwestern University)

  • Iannis Aifantis

    (NYU School of Medicine
    NYU School of Medicine)

  • Aristotelis Tsirigos

    (NYU School of Medicine
    NYU School of Medicine
    NYU School of Medicine)

Abstract

The metazoan genome is compartmentalized in areas of highly interacting chromatin known as topologically associating domains (TADs). TADs are demarcated by boundaries mostly conserved across cell types and even across species. However, a genome-wide characterization of TAD boundary strength in mammals is still lacking. In this study, we first use fused two-dimensional lasso as a machine learning method to improve Hi-C contact matrix reproducibility, and, subsequently, we categorize TAD boundaries based on their insulation score. We demonstrate that higher TAD boundary insulation scores are associated with elevated CTCF levels and that they may differ across cell types. Intriguingly, we observe that super-enhancers are preferentially insulated by strong boundaries. Furthermore, we demonstrate that strong TAD boundaries and super-enhancer elements are frequently co-duplicated in cancer patients. Taken together, our findings suggest that super-enhancers insulated by strong TAD boundaries may be exploited, as a functional unit, by cancer cells to promote oncogenesis.

Suggested Citation

  • Yixiao Gong & Charalampos Lazaris & Theodore Sakellaropoulos & Aurelie Lozano & Prabhanjan Kambadur & Panagiotis Ntziachristos & Iannis Aifantis & Aristotelis Tsirigos, 2018. "Stratification of TAD boundaries reveals preferential insulation of super-enhancers by strong boundaries," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03017-1
    DOI: 10.1038/s41467-018-03017-1
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    Cited by:

    1. Xiao Ge & Haiyan Huang & Keqi Han & Wangjie Xu & Zhaoxia Wang & Qiang Wu, 2023. "Outward-oriented sites within clustered CTCF boundaries are key for intra-TAD chromatin interactions and gene regulation," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Jin H. Yang & Hugo B. Brandão & Anders S. Hansen, 2023. "DNA double-strand break end synapsis by DNA loop extrusion," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Olivier Messina & Flavien Raynal & Julian Gurgo & Jean-Bernard Fiche & Vera Pancaldi & Marcelo Nollmann, 2023. "3D chromatin interactions involving Drosophila insulators are infrequent but preferential and arise before TADs and transcription," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Claire Marchal & Nivedita Singh & Zachary Batz & Jayshree Advani & Catherine Jaeger & Ximena Corso-Díaz & Anand Swaroop, 2022. "High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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