Volume 24, No 5, May 2014

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 24 Issue 5, May 2014: 513-531   |  Open Access

ORIGINAL ARTICLES

Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus

Jian-Feng Xiang¹, Qing-Fei Yin¹, Tian Chen¹, Yang Zhang¹, Xiao-Ou Zhang², Zheng Wu¹, Shaofeng Zhang¹, Hai-Bin Wang³, Junhui Ge³, Xuhua Lu³, Li Yang² and Ling-Ling Chen¹

¹State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, 320 Yueyang Road, Shanghai 200031, China
²Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China
³Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China Correspondence: Ling-Ling Chen,(linglingchen@sibcb.ac.cn)

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.

10.1038/cr.2014.35

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