In situ and in vitro evidence for intragenic binding of nuclear factors at the murine c-myc locus.

A block to transcriptional elongation within the c-myc proto-oncogene has been previously observed in a large number of different mouse and human cell types and its release is a potentially important element in the pathogenesis of some malignancies. We show here that the chromatin around the mouse c-myc exon 1-intron 1 boundary is differentially accessible to restriction enzymes in purified nuclei. Using a combination of in situ exonuclease III protection assay with in vitro footprints and gel band shifts, we have shown the existence of a stable nucleoprotein complex in this same region in mouse erythroleukemia cell nuclei. This situation is not peculiar to these cells and we have shown that the accessibility of the two BglII sites present at the beginning of intron 1 seems to depend not only upon the transcriptional state, but also upon the structural integrity of the gene.