title: Transcriptional amplification in tumor cells with elevated c-Myc.
abstract: Elevated expression of the c-Myc transcription factor occurs frequently in human cancers and is associated with tumor aggression and poor clinical outcome. The effect of high levels of c-Myc on global gene regulation is poorly understood but is widely thought to involve newly activated or repressed "Myc target genes." We report here that in tumor cells expressing high levels of c-Myc the transcription factor accumulates in the promoter regions of active genes and causes transcriptional amplification, producing increased levels of transcripts within the cell's gene expression program. Thus, rather than binding and regulating a new set of genes, c-Myc amplifies the output of the existing gene expression program. These results provide an explanation for the diverse effects of oncogenic c-Myc on gene expression in different tumor cells and suggest that transcriptional amplification reduces rate-limiting constraints for tumor cell growth and proliferation.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge Center, MA 02142, USA.
authors.forename: Charles Y
authors.initials: CY
authors.lastname: Lin
authors.forename: Jakob
authors.initials: J
authors.lastname: Lovén
authors.forename: Peter B
authors.initials: PB
authors.lastname: Rahl
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Paranal
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Burge
authors.forename: James E
authors.initials: JE
authors.lastname: Bradner
authors.forename: Tong Ihn
authors.initials: TI
authors.lastname: Lee
authors.forename: Richard A
authors.initials: RA
authors.lastname: Young
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004742:Enhancer Elements, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc