EXPRESSION AND REGULATION OF THE DYSTROPHIN PURKINJE PROMOTER IN HUMAN SKELETAL-MUSCLE, HEART, AND BRAIN

Dystrophin mRNA transcripts from the P (Purkinje) promoter were shown to be differentially expressed in human skeletal muscle, heart, and br ain. The expression pattern was characteristic of tissue type and deve lopmental stage. Polymerase chain reaction (PCR) analysis of the P pro moter transcripts in adult skeletal muscle and adult brain identified two alternatively spliced sequences, one that encodes a full-length dy strophin mRNA and a second that transcribes a termination codon 27 nuc leotides (8 amino acids) after the ATG initiation site. Alternative sp licing of this truncated coding transcript was developmentally regulat ed, and it was expressed as the major form in adult cortical brain and adult heart. The biological significance of this peptide remains uncl ear. The full-length transcript was the major form in fetal cortical b rain and adult skeletal muscle. Ribonuclease protection assay demonstr ated that as much as 20% of dystrophin transcription in normal adult s keletal muscle was derived from the full-length transcript from the P promoter. In contrast, adult heart did not express significant levels of P promoter derived transcripts. Thus, transcripts from the P promot er were found to be developmentally regulated in the brain, and its ac tivity was differentially expressed in skeletal verses cardiac muscle tissues. These data shaw that the P promoter transcript displays a bro ader scope of expression, regulation, and complexity than previously a ppreciated.