A Distal Upstream Enhancer from the Myelin Basic Protein Gene Regulates Expression in Myelin-Forming Schwann Cells

• Published in: The Journal of neuroscience Vol. 21; no. 11; pp. 3780 - 3787
• Main Authors: Forghani, Reza, Garofalo, Lorella, Foran, David R, Farhadi, Hooman F, Lepage, Pierre, Hudson, Thomas J, Tretjakoff, Irene, Valera, Priscila, Peterson, Alan
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01.06.2001; Society for Neuroscience
• Subjects: Animals; beta-Galactosidase - biosynthesis; beta-Galactosidase - genetics; Binding Sites - genetics; DNA-Binding Proteins - metabolism; Early Growth Response Protein 2; Enhancer Elements, Genetic - genetics; Gene Expression Regulation, Developmental; Genes, Reporter; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Transgenic; Mutagenesis, Site-Directed; Myelin Basic Protein - biosynthesis; Myelin Basic Protein - genetics; Myelin Sheath - genetics; Myelin Sheath - metabolism; Peripheral Nerves - cytology; Peripheral Nerves - embryology; Peripheral Nerves - metabolism; Promoter Regions, Genetic; Regulatory Sequences, Nucleic Acid; RNA, Messenger - biosynthesis; Schwann cell enhancer 1; Schwann Cells - cytology; Schwann Cells - metabolism; Sequence Analysis, DNA; Spinal Cord - cytology; Spinal Cord - metabolism; Transcription Factors - metabolism; Transgenes
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.21-11-03780.2001

In peripheral nerves, large caliber axons are ensheathed by myelin-elaborating Schwann cells. Multiple lines of evidence demonstrate that expression of the genes encoding myelin structural proteins occurs in Schwann cells in response to axonal instructions. To gain further insight into the mechanisms controlling myelin gene expression, we used reporter constructs in transgenic mice to search for the DNA elements that regulate the myelin basic protein (MBP) gene. Through this in vivo investigation, we provide evidence for 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 addition, robust targeting activity conferred by SCE1 was shown to be independent of other MBP 5' flanking sequence. These observations suggest that SCE1 will make available a powerful tool to drive transgene expression in myelinating Schwann cells and that a focused analysis of the SCE1 sequence will lead to the identification of transcription factor binding sites that positively regulate MBP expression.