Stratification of TAD boundaries reveals preferential insulation of super-enhancers by strong boundaries
| Autor: | Panagiotis Ntziachristos, Aristotelis Tsirigos, Theodore Sakellaropoulos, Aurelie C. Lozano, Prabhanjan Kambadur, Charalampos Lazaris, Iannis Aifantis, Yixiao Gong |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Epigenomics CCCTC-Binding Factor Science General Physics and Astronomy General Biochemistry Genetics and Molecular Biology Article Machine Learning 03 medical and health sciences Neoplasms Medicine and Health Sciences Animals Humans Enhancer lcsh:Science Insulator Element Boundary strength Physics Contact matrix Multidisciplinary Extramural Biology and Life Sciences General Chemistry Chromatin Gene Expression Regulation Neoplastic 030104 developmental biology Enhancer Elements Genetic CTCF Evolutionary biology Insulator Elements lcsh:Q |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-12 (2018) NATURE COMMUNICATIONS Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-03017-1 |
| Popis: | 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. Topologically associating domains (TADs) detected by Hi-C technologies are megabase-scale areas of highly interacting chromatin. Here Gong, Lazaris et al. develop a computational approach to improve the reproducibility of Hi-C contact matrices and stratify TAD boundaries based on their insulating strength. |
| Databáze: | OpenAIRE |
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