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

Cell Res. 2014 May;24(5):513-31. doi: 10.1038/cr.2014.35. Epub 2014 Mar 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCCTC-Binding Factor
  • Cell Line, Tumor
  • Chromatin / chemistry
  • Chromatin / metabolism*
  • Colon / metabolism
  • Colon / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Genes, myc
  • Genetic Loci
  • Humans
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-myc / genetics*
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Rectum / metabolism
  • Rectum / pathology
  • Repressor Proteins / metabolism

Substances

  • CCAT1 long noncoding RNA, human
  • CCCTC-Binding Factor
  • CTCF protein, human
  • Chromatin
  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • Repressor Proteins

Associated data

  • GEO/GSE55259
  • GEO/GSE55261