Regulatory elements that modulate expression of human c-myc.

Regulation of transcription from the proto-oncogene c-myc apparently plays an important part in cellular proliferation and the genesis of diverse tumors. Here, we report that the abundance of transcripts from the two principal promoters for human c-myc (P1 and P2) is governed by a composite of positive and negative regulators, located within a 2.3-kb domain upstream of the gene. In actively proliferating cells, the action of the positive elements is apparently dominant over that of the single negative regulator that we have identified. Nuclear proteins bind specifically to nucleotide sequences within the negative regulator and at least one of the positive regulators. The cooperative and counteracting actions of the regulatory elements described here presumably contribute to the plasticity of transcription from c-myc and may be affected by the tumorigenic damage that sometimes afflicts c-myc.