title: Repression of myelin proteolipid protein gene expression is mediated through both general and cell type-specific negative regulatory elements in nonexpressing cells.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR 72205, USA.
authors.forename: Shenyang
authors.initials: S
authors.lastname: Li
authors.forename: Anna
authors.initials: A
authors.lastname: Dobretsova
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Kokorina
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Wight
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D018983:DNA Footprinting; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000502:physiology*; D017930:Genes, Reporter; D007438:Introns / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000502:physiology*; D017384:Sequence Deletion; D014162:Transfection
chemical_list: D020121:5' Untranslated Regions; D018991:Myelin Proteolipid Protein; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins