Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Department of Orthopedic Surgery, National University Health Systems (NUHS), Singapore, Singapore.
Sci Rep. 2017 May 19;7(1):2186. doi: 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.
伸展的组蛋白区域，如超级增强子和广泛的 H3K4me3 结构域，与维持细胞身份和癌症有关。我们将 K562 慢性髓系白血病细胞系和 MCF-7 乳腺癌细胞系中的超级增强子和广泛的 H3K4me3 结构域与染色质相互作用联系起来。超级增强子和广泛的 H3K4me3 结构域与染色质相互作用的相关性高于其典型对应物。有趣的是，我们确定了一组与广泛的 H3K4me3 结构域重叠且与包括肿瘤抑制基因在内的癌症相关基因高度相关的超级增强子。除了细胞系之外，我们还可以通过基于染色体构象捕获（3C）的方法在原代人类样本中观察到染色质相互作用。一些涉及超级增强子和广泛的 H3K4me3 结构域的染色质相互作用是组成性的，可在癌症和正常样本中找到。总之，这些结果揭示了超级增强子和广泛的 H3K4me3 结构域在基因调控方面的新复杂性。
