Cao, F., Fang, Y., Tan, H.K. et al. Super-Enhancers and Broad H3K4me3 Domains Form Complex Gene Regulatory Circuits Involving Chromatin Interactions. Sci Rep 7, 2186 (2017). https://doi.org/10.1038/s41598-017-02257-3
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.
We would like to thank Liang Piu Koh, Tung Moon Ley and Ng Chin Hin, all of Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, for collecting patient samples, as well as members of the Leukemia Cell Bank core, particularly Elaine Seah and Cayden Pang for help in organizing the samples. We would like to thank Tng Jia Qi and Meital Hatan from the Cancer Science Institute for technical help, and help in organizing the samples and administrative matters. We would like to thank the staff of Oxford Biodynamics for assistance with the EpiSwitch™ analysis, including Chloe Bird. We would like to thank all members of the Fullwood Lab for helpful comments. This research is supported by the National Research Foundation (NRF) Singapore through an NRF Fellowship awarded to M.J.F (NRF-NRFF2012-054), and Yale-NUS start-up funds awarded to M.J.F. This research is supported by the Singapore Ministry of Health’s National Medical Research Council under its Singapore Translational Research (STaR) Investigator Award (to D.G.T.). This research is supported by the RNA Biology Center at the Cancer Science Institute of Singapore, NUS, as part of funding under the Singapore Ministry of Education Academic Research Fund Tier 3 awarded to D.G.T (MOE2014-T3-1-006). This research is supported by the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative.