title: DKC1 is a direct and conserved transcriptional target of c-MYC.
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.
authors.affiliation: School of Dental Medicine, University of Pennsylvania, Department of Pathology, 240 South 40th Street, Philadelphia, PA 19104, USA. falawi@path.dental.upenn.edu
authors.forename: Faizan
authors.initials: F
authors.lastname: Alawi
authors.forename: Megan N
authors.initials: MN
authors.lastname: Lee
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics*; D002460:Cell Line; D017124:Conserved Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D018390:Gene Targeting / Q000379:methods*; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*