Chromatin structure of the murine c-myc locus: implications for the regulation of normal and chromosomally translocated genes.

To assess possible alterations of c-myc transcriptional control in murine B-cell tumors, we have investigated the pattern of DNaseI hypersensitive sites in the gene's putative regulatory region and within the gene in a variety of genomic contexts. A number of such sites were found in several cell types, but none of these was detectable in a gene which was shown to be transcriptionally silent by the criterion of elongation of nascent transcripts in isolated nuclei. These results differ from those of a previous study, in which a DNaseI-hypersensitive site approximately 2 kb upstream of the gene was proposed to be associated with negative regulation of c-myc transcription in human cells. An analysis of DNA sequences presented here reveals that this region is highly homologous between mouse and human, suggesting that these upstream hypersensitive sites do not reflect species-specific regulatory elements. We also present data indicating that this hypersensitive site distinguishes the c-myc alleles in translocation-positive plasma cell tumors which lack c-myc rearrangement. Furthermore, we report the existence of hypersensitive sites within the gene. One of these appears to be associated with cryptic promoters that are employed only when the normal promoters are lost as a consequence of chromosome translocation. These results are discussed in the context of c-myc translocation and gene breakage and with respect to possible stage-specific regulation of the gene's transcriptional competence.