Super-Enhancers and Broad H3K4me3 Domains Form Complex Gene Regulatory Circuits Involving Chromatin Interactions

• Main Authors: Cao, Fan, Fang, Yiwen, Tan, Hong Kee, Goh, Yufen, Choy, Jocelyn Yeen Hui, Koh, Bryan Thean Howe, Hao Tan, Jiong, Bertin, Nicolas, Ramadass, Aroul, Hunter, Ewan, Green, Jayne, Salter, Matthew, Akoulitchev, Alexandre, Wang, Wilson, Chng, Wee Joo, Tenen, Daniel G., Fullwood, Melissa Jane
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2017
• Subjects: Chronic myeloid leukaemia; Genome informatics
• Online Access: https://hdl.handle.net/10356/83768; http://hdl.handle.net/10220/42747
• Institution: Nanyang Technological University

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.