Independent research groups led by Drs. Robert Eisenman (Fred Hutchinson Cancer Center) and Bruno Amati (European Institute of Oncology) report on the first genome-wide analyses of in vivo Myc targets in the Drosophila and human genomes, respectively. As the myc gene is mutated in approximately one-third of all human cancers, the identification of the full range of genes that interact with Myc under normal conditions will be important to understanding how abnormal myc expression can lead to cancer.
The myc gene encodes a transcription factor (Myc) that, together with a partner protein (Max), binds to specific DNA sequences to regulate gene expression. myc is classified as an oncogene because genetic mutations that result in over-expression of Myc protein promote unregulated cell proliferation and cancer. While Myc has an established role in directing cell growth, proliferation, differentiation, and death, the precise molecular pathways of Myc action are still largely unknown.
"A major problem in understanding how Myc exerts its profound effects on cellular functions has been the determination of the nature and number of its binding sites on DNA," states Dr. Eisenman. Previous attempts to identify Myc-regulated genes have provided incomplete pictures of Myc targets, complicated by such issues as direct versus indirect interactions and physiological relevance.
These two papers represent a significant advance in the effort to identify DNA sequences that bind Myc. Using completely different experimental approaches and biological systems, both research teams arrived at a similar result: Myc binds to ~10% of all genes.