C-myc plays an important role in cellular proliferation. Its membership in the helix-loop-helix family of genes, as well as the recent discovery of its ability to bind as a heterodimer with Max, suggests that this dimer may act as a transcription factor. Such a dimeric transcription factor complex may impart to c-myc a specificity for DNA binding to the sequence CACGTG. In addition to acting as a transcription factor, c-myc appears to regulate genes expressed in the GO/G1 transition. We have previously demonstrated this effect with two such GO/G1 genes. In order to identify additional genes whose expression is regulated by c-myc, we have constructed orientation-specific cDNA libraries for cell lines which differ only in their ability to express an exogenously transfected c-myc construct in response to heat shock. A method of cDNA subtraction which we developed for colon carcinoma (see Project ZOICPO5585-03 LMO) will be used here to enrich for cDNAs uniquely co-expressed with c-myc, as well as cDNAs whose expression may be down- regulated by c-myc. Co-expressed genes are expected to include proliferation-specific genes, as well as some genes that may repress differentiation. Down-regulated genes may include certain key differentiation-inducing genes of the homeobox class.
