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

By Jian-Feng Xiang, Qing-Fei Yin, Tian Chen, Yang Zhang, Xiao-Ou Zhang, Zheng Wu, Shaofeng Zhang, Hai-Bin Wang, Junhui Ge, Xuhua Lu and 2 more. Cell Research, 2014

642 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8cd309d737a8b11061ffeb11554be2f37c5314f7

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Citations in the corpus

Lnc2Cancer: a manually curated database of experimentally supported lncRNAs associated with various human cancers (2015, background): “In addition to these large-scale studies, studies focused on individual or specific lncRNA in various cancers are rapidly emerging (20,21).”
Long Non-Coding RNA in the Pathogenesis of Cancers (2019, background): “CCAT1 promotes c-Myc expression by inhibition of the MAPK pathway [286], and c-Myc can also promote CCAT1 transcription via binding to its promoter region [284].”
Genomic positional conservation identifies topological anchor point (tap)RNAs linked to developmental loci (2016, background): “…the binding of transcription factors, Mediator and CTCF complexes (Deng et al., 2016; Hacisuleyman et al., 2014; Kung et al., 2015; Lai et al., 2013; Minajigi et al., 2015; Sun et al., 2014; Wang et al., 2014a; Wang et al., 2011; Xiang et al., 2014; Yang et al., 2015; Zhang et al., 2014).”
Linking Long Noncoding RNA Localization and Function. (2016, background): “Strikingly, CCAT1-L accumulates in cis in the nucleus while CCAT1-S is mainly cytoplasmic [13], indicating that the prevalence of altered 30 end formation of Pol II transcripts in mammals [54] may promote different lncRNP assemblies for lncRNA localization.”
Long Noncoding RNAs in Cardiovascular Diseases (2015, neutral): “By interacting with CCCTC-binding factor, which binds to a transcriptional insulator element, CCAT1-L participates in the chromatin looping formation in the MYC promoter.(41) Because the median size of super enhancer is 19.”