TRANSCRIPTIONAL REGULATION OF THE N-MYC GENE - IDENTIFICATION OF POSITIVE REGULATORY ELEMENT AND ITS DOUBLE-STRANDED AND SINGLE-STRANDED-DNA BINDING-PROTEINS

The N-myc gene is amplified and overexpressed in neuroblastoma, retino blastoma and small cell lung carcinoma, and is considered to be relate d to cell proliferation and/or differentiation. The transcriptional re gulatory sequences of the c-myc gene have been already identified, whi le those of N-myc have remained obscure for a long time. In this repor t, we have identified several positive and negative transcriptional re gulatory elements in the upstream region of the mouse N-myc gene. Amon g them, an activating sequence spanning - 860 to - 797 bp (63 bp) coul d be reduced to a functional core of 21 bp from - 846 to - 826. This s equence, termed N21 box, worked as a positive transcriptional element when linked directly upstream (but not downstream) of the putative N-m yc promoter in HeLa, not in IMR32 cells. At least two proteins, of 42 kDa and 100 kDa, bound to the double-stranded N21 box, and were expres sed in HeLa as well as in IMR32 cells. Moreover, the plus strand of N2 1 box could be specifically bound by a species of 42 kDa from either c ell type and by a 37 kDa protein found only in HeLa cells. These prote ins may be factors binding to positive transcriptional regulatory elem ents and may have a role in the regulation of N-myc expression.