Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus
Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus
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DOI：
10.1038/cr.2014.117
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发表时间：
2014-09
期刊：
影响因子：
44.1
通讯作者：
Jian-Feng Xiang;Qing-Fei Yin;Tian Chen;Yang Zhang;Xiao-Ou Zhang;Zheng Wu;Shaofeng Zhang;Hai-Bin Wang;Junhui Ge;Xuhua Lu;Li Yang;Ling-Ling Chen-Ling
中科院分区：
文献类型：
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作者：
Jian-Feng Xiang;Qing-Fei Yin;Tian Chen;Yang Zhang;Xiao-Ou Zhang;Zheng Wu;Shaofeng Zhang;Hai-Bin Wang;Junhui Ge;Xuhua Lu;Li Yang;Ling-Ling Chen-Ling
人类8 q24基因沙漠包含多个增强子，这些增强子与MYC癌基因形成组织特异性的长距离染色质环，但对MYC基因座上的染色质环是如何调节的仍然知之甚少。在这里，我们证明了一个长的非编码RNA（lncRNA），CCAT 1-L，是转录特异性在人类结直肠癌的基因座515 kb的上游MYC。这种lncRNA在MYC转录调控中起作用，并促进长距离染色质循环。重要的是，CCAT 1-L基因座位于强超级增强子内，并且在空间上接近MYC。CCAT 1-L的敲低降低了MYC启动子及其增强子之间的长程相互作用。此外，CCAT 1-L与CTCF相互作用并调节这些环区域的染色质构象。这些结果揭示了一个以前未注释的lncRNA在MYC基因座的基因调控中的重要作用。
The human 8q24 gene desert contains multiple enhancers that form tissue-specific long-range chromatin loops with the MYC oncogene, but how chromatin looping at the MYC locus is regulated remains poorly understood. Here we demonstrate that a long noncoding RNA (lncRNA), CCAT1-L, is transcribed specifically in human colorectal cancers from a locus 515 kb upstream of MYC. This lncRNA plays a role in MYC transcriptional regulation and promotes long-range chromatin looping. Importantly, the CCAT1-L locus is located within a strong super-enhancer and is spatially close to MYC. Knockdown of CCAT1-L reduced long-range interactions between the MYC promoter and its enhancers. In addition, CCAT1-L interacts with CTCF and modulates chromatin conformation at these loop regions. These results reveal an important role of a previously unannotated lncRNA in gene regulation at the MYC locus.