Adrenal medullary chromaffin cells have the capacity to transdifferentiate into sympathetic neurons. We show here that SCG10, a neural-specific gene that is induced during this transdifferentiation, is maintained in mature chromaffin cells in a potentially active chromatin conformation marked by two DNAase I hypersensitive sites (HSS). A low level of transcription is associated with this conformation. The HSS are also present in neurons expressing high levels of SCG10, but not in nonneuronal cells. Experiments using transgenic mice suggest that these HSS can in principle form in any cell type expressing the gene, but that a cis-repression mechanism normally prevents their assembly in nonneuronal cells. We suggest that the SCG10 HSS may represent a molecular marker of the lineage and phenotypic plasticity of chromaffin cells.