C-MYC SELECTIVELY REGULATES THE LATENT PERIOD AND ERYTHROID-SPECIFIC GENES IN MURINE ERYTHROLEUKEMIA CELL-DIFFERENTIATION

During the latent period of murine erythroleukemia (MEL) cell differentiation, c-myc levels showed a significant change and the overexpression of the transferred c-myc gene inhibited the commitment and differentiation of MEL cells, suggesting that c-Myc may be a key molecule for the commitment. Since c-Myc may function as a DNA binding transcription factor, we examined whether c-Myc regulates the latent period genes (hsp and hsc70, MER5, Id and Spi-1 genes) and the erythroid-specific genes [beta-globin, glycophorin, delta-aminolevulinic acid synthase (ALAS-E), GATA-1 and erythropoietin receptor (EpoR)] in the MEL cell transformant having transferred c-myc gene. The overexpression of c-myc gene affected the latent period genes in different ways: hsc and hsp 70 genes and Id gene were positively regulated, while expression of MER5 gene was repressed. While c-myc is thought to be involved in DNA replication, its overexpression showed no effect on the expression of proliferating cell specific nuclear antigen or DNA polymerase alpha. The overexpression of c-myc repressed the expression of glycophorin, ALAS-E and beta-globin genes, of the five erythroid-specific genes, but had no effect on expression of GATA-1 or EpoR gene. These results suggest that c-Myc differentially regulates the expression of the latent period and erythroid-specific genes.