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

78Citations
Citations of this article
256Readers
Mendeley users who have this article in their library.

This article is free to access.

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.

Cite

CITATION STYLE

APA

Gong, Y., Lazaris, C., Sakellaropoulos, T., Lozano, A., Kambadur, P., Ntziachristos, P., … Tsirigos, A. (2018). Stratification of TAD boundaries reveals preferential insulation of super-enhancers by strong boundaries. Nature Communications, 9(1). https://doi.org/10.1038/s41467-018-03017-1

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free