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Super-Enhancers and Broad H3K4me3 Domains Form Complex Gene Regulatory Circuits Involving Chromatin Interactions. (Sci Rep, May 2017)

Cao F1, Fang Y1, Tan HK1, Goh Y1, Choy JYH1, Koh BTH2, Hao Tan J2, Bertin N1,3, Ramadass A4, Hunter E4, Green J4, Salter M4, Akoulitchev A4, Wang W2, Chng WJ1,5,6, Tenen DG1, Fullwood MJ7,8,9,10.

Author information
1 Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
2 Department of Orthopedic Surgery, National University Health Systems (NUHS), Singapore, Singapore.
3 Human Longevity Singapore Pte. Ltd., Singapore, Singapore.
4 Oxford BioDynamics Plc, Oxford, England, UK.
5 National University Cancer Institute, National University Health System, Singapore, Singapore.
6 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
7 Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
8 School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
9 Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore,Singapore.
10 Yale-NUS Liberal Arts College, Singapore, Singapore.

Abstract
Stretched histone regions, such as super-enhancers and broad H3K4me3 domains, are associated with maintenance of cell identity and cancer. We connected super-enhancers and broad H3K4me3 domains in the K562 chronic myelogenous leukemia cell line as well as the MCF-7 breast cancer cell line with chromatin interactions. Super-enhancers and broad H3K4me3 domains showed higher association with chromatin interactions than their typical counterparts. Interestingly, we identified a subset of super-enhancers that overlap with broad H3K4me3 domains and show high association with cancer-associated genes including tumor suppressor genes. Besides cell lines, we could observe chromatin interactions by a Chromosome Conformation Capture (3C)-based method, in primary human samples. Several chromatin interactions involving super-enhancers and broad H3K4me3 domains are constitutive and can be found in both cancer and normal samples. Taken together, these results reveal a new layer of complexity in gene regulation by super-enhancers and broad H3K4me3 domains.

PMID: 28526829