Potentiation of myelin proteolipid protein (Plp) gene expression is mediated through AP-1-like binding sites
Article first published online: 30 JUL 2004
Journal of Neurochemistry
Volume 90, Issue 6, pages 1500–1510, September 2004
How to Cite
Dobretsova, A., Kokorina, N. A. and Wight, P. A. (2004), Potentiation of myelin proteolipid protein (Plp) gene expression is mediated through AP-1-like binding sites. Journal of Neurochemistry, 90: 1500–1510. doi: 10.1111/j.1471-4159.2004.02683.x
- Issue published online: 16 AUG 2004
- Article first published online: 30 JUL 2004
- Received March 29, 2004; revised manuscript received May 21, 2004; accepted May 31, 2004.
- AP-1 response element;
- gene expression;
- myelin proteolipid protein gene
The myelin proteolipid protein (Plp) gene is expressed in oligodendrocytes and encodes the most abundant protein found in mature CNS myelin. Expression of the gene is dynamic and peaks during the active myelination period of CNS development. The surge in Plp gene activity during this period has been purported to be mediated by a positive regulatory region located within the first intron. This region, designated ASE for antisilencer/enhancer, is located approximately 1 kb downstream of exon 1 sequences and encompasses nearly 100 bp. However, neither the critical nucleotides within this region, nor the associated DNA-binding proteins have been identified. In the present study, DNase I footprinting analysis demonstrated widespread protection of the region on both the coding and non-coding strands suggesting that multiple transcription factors are likely involved. Targeting of putative DNA-protein binding sites contained within the ASE by gel shift, transfection and mutagenesis studies revealed the importance of several AP-1-like binding sites in governing high levels of Plp gene expression in oligodendrocytes. Our results suggest that factors, which bind to these sites, form the core of a multiprotein complex that assembles on the ASE and ultimately affects the temporal regulation of the gene in oligodendrocytes.