title: Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus.
abstract: 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.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Qing-Fei
authors.initials: QF
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key 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.
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Wang
authors.affiliation: Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Ge
authors.affiliation: Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Xuhua
authors.initials: X
authors.lastname: Lu
authors.affiliation: Key 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.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Chen
mesh_terms: D000076246:CCCTC-Binding Factor; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004742:Enhancer Elements, Genetic; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D016259:Genes, myc; D056426:Genetic Loci; D006801:Humans; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: C579842:CCAT1 long noncoding RNA, human; D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; D012097:Repressor Proteins