A distal upstream enhancer from the myelin basic protein gene regulates expression in myelin-forming schwann cells

In peripheral nerves, large caliber axons are ensheathed by myelin-elaborat ing Schwann cells. Multiple lines of evidence demonstrate that expression o f the genes encoding myelin structural proteins occurs in Schwann cells in response to axonal instructions. To gain further insight into the mechanism s controlling myelin gene expression, we used reporter constructs in transg enic mice to search for the DNA elements that regulate the myelin basic pro tein (MBP) gene. Through this in vivo investigation, we provide evidence fo r the participation of multiple, widely distributed, positive and negative elements in the overall control of MBP expression. Notably, all constructs bearing a 0.6 kb far-upstream sequence, designated Schwann cell enhancer 1 (SCE1), expressed at high levels in myelin-forming Schwann cells. In additi on, robust targeting activity conferred by SCE1 was shown to be independent of other MBP 5' flanking sequence. These observations suggest that SCE1 wi ll make available a powerful tool to drive transgene expression in myelinat ing Schwann cells and that a focused analysis of the SCE1 sequence will lea d to the identification of transcription factor binding sites that positive ly regulate MBP expression.