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Antisilencing
Author(s) -
Dobretsova Anna,
Wight Patricia A.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0722227.x
Subject(s) - proteolipid protein 1 , biology , gene , intron , myelin proteolipid protein , regulatory sequence , regulation of gene expression , gene expression , transcription (linguistics) , psychological repression , myelin , genetics , transgene , microbiology and biotechnology , myelin basic protein , central nervous system , linguistics , philosophy , neuroscience
Antisilencer or antirepressor elements have beendescribed, thus far, for only a few eukaryotic genes and were identified bytheir ability not to augment gene expression per se but to override repressionmediated via negative transcription regulatory elements. Here we report thefirst case of antisilencing for a neural‐specific gene, the myelin proteolipidprotein (PLP) gene ( Plp ). PLP is the most abundant protein found inCNS myelin. The protein is synthesized in oligodendrocytes, and its expressionis regulated developmentally. Previously we have shown that aPLP‐ lacZ transgene (which includes the entire sequence for Plp intron 1) is regulated in mice, in a manner consistent with thespatial and temporal expression of the endogenous Plp gene. In thepresent report, we demonstrate by transfection analyses, using variousPLP‐ lacZ deletion constructs, that Plp intron 1 DNA containsmultiple elements that collectively regulate Plp gene expression inoligodendrocytes. One of these regulatory elements functions as anantisilencer element, which acts to override repression mediated by at leasttwo negative regulatory elements located elsewhere within Plp intron 1 DNA. The mechanism for antisilencing appears to be complex as the intragenic region that mediates this function binds multiple nuclear factors specifically.