The dystrophin lymphocyte promoter revisited: 4.5-megabase intron, or artefact?

The human dystrophin gene has seven generally recognised promoters and one, the so-called lymphocyte promoter, whose status remains uncertain. We re-evaluated this promoter in the light of recently available human and mouse genome sequences, and attempted to compare its activity in lymphocytes with that of the muscle promoter. We find that the lymphocyte promoter lies immediately adjacent to the chronic granulomatous disease gene, CYBB, approximately 4.5 megabases upstream of dystrophin exon 2. This makes the supposed lymphocyte dystrophin primary transcript 7 megabases in size, with an expected transcription time in excess of 2 days. We also find that lymphocyte promoter use in peripheral blood lymphocytes is negligible compared to that of the muscle promoter in the same tissue. Together with the presence in the intron of a sense-strand multi-exon gene, and lack of conserved linkage in the mouse, we propose that the lymphocyte promoter is not a biologically significant part of the dystrophin gene.