Repression of myelin proteolipid protein gene expression is mediated through both general and cell type-specific negative regulatory elements in nonexpressing cells
Article first published online: 25 JUN 2002
Journal of Neurochemistry
Volume 82, Issue 1, pages 159–171, July 2002
How to Cite
Li, S., Dobretsova, A., Kokorina, N. A. and Wight, P. A. (2002), Repression of myelin proteolipid protein gene expression is mediated through both general and cell type-specific negative regulatory elements in nonexpressing cells. Journal of Neurochemistry, 82: 159–171. doi: 10.1046/j.1471-4159.2002.00962.x
- Issue published online: 25 JUN 2002
- Article first published online: 25 JUN 2002
- Received February 28, 2002; revised manuscript received April 5, 2002; accepted April 8, 2002.
- cell type-specific gene expression;
- gene regulation;
- myelin proteolipid protein gene;
- negative regulatory element
The myelin proteolipid protein gene (Plp) is expressed primarily in oligodendrocytes. Yet how the gene remains repressed in nonexpressing cells has not been defined, and potentially could cause adverse effects in an organism if the mechanism for repression was impaired. Previous studies suggest that the first intron contains element(s), which suppress expression in nonexpressing cells, although the identity of these elements within the 8 kb intron was not characterized. Here we report the localization of multiple negative regulatory elements that repress Plp gene expression in nonexpressing cells (+/+ Li). Two of these elements (regions) correspond to those used by Plp expressing cells (N20.1), whilst another acts in a cell type-specific manner (i.e. operational in +/+ Li liver cells, but not N20.1 cells). By gel-shift and DNase I footprinting analyses, the factor(s) that bind to the cell type-specific negative regulatory region appear to be far more abundant in +/+ Li cells than in N20.1 cells. Thus, Plp gene repression is mediated through the combinatorial action of both ‘general’ and cell type-specific negative regulatory elements. Additionally, repression in +/+ Li cells cannot be overcome via an antisilencer/enhancer element, which previously has been shown to function in N20.1 cells.