DKC1 Is a Direct and Conserved Transcriptional Target of c-MYC

Biochem Biophys Res Commun. 2007 Nov 3;362(4):893-8. doi: 10.1016/j.bbrc.2007.08.071. Epub 2007 Aug 24.

Abstract

Recent studies have identified upregulation of the dyskeratosis congenita 1 (DKC1) gene in association with various sporadic cancers. Whole genome analyses have suggested that DKC1 may be regulated by the c-MYC oncoprotein. c-MYC is among the most commonly deregulated proteins in human cancer. However, controversy remains as to whether DKC1 is a direct or indirect target of c-MYC. Using human and rodent cell lines expressing conditionally active c-MYC transgenes, we show that c-MYC activation is associated with relatively acute induction of DKC1 expression. Chromatin immunoprecipitation assays reveal c-MYC binding to two distinct, phylogenetically conserved regions within the DKC1 promoter and intron one. We further demonstrate that c-MYC-mediated Dkc1 transcription can occur in the absence of de novo protein synthesis. These data indicate that DKC1 is a direct and conserved transcriptional target of c-MYC, and suggest a biologic basis for DKC1 overexpression in neoplasia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics*
  • Cell Line
  • Conserved Sequence / genetics
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation / genetics
  • Gene Targeting / methods*
  • Genes, myc / genetics*
  • Humans
  • Nuclear Proteins / genetics*
  • Transcription Factors / genetics*
  • Transcription, Genetic / genetics*
  • Transcriptional Activation / genetics*

Substances

  • Cell Cycle Proteins
  • DKC1 protein, human
  • DNA-Binding Proteins
  • MYCBP protein, human
  • Nuclear Proteins
  • Transcription Factors