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

Yixiao Gong, Charalampos Lazaris, Theodore Sakellaropoulos, Aurelie Lozano, Prabhanjan Kambadur, Panagiotis Ntziachristos, Iannis Aifantis () and Aristotelis Tsirigos ()
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Yixiao Gong: NYU School of Medicine
Charalampos Lazaris: 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
Aristotelis Tsirigos: NYU School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03017-1

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DOI: 10.1038/s41467-018-03017-1

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