Intron 1 Is Required for Cell Type-Specific, But Not Injury-Responsive, Peripherin Gene Expression

The "primitive" neurons of the peripheral nervous system (PNS) have the remarkable ability to regenerate new fibers. This regenerative process requires a sequence of gene activation and repression that is poorly understood. One gene that is almost exclusively expressed in neurons of the PN...

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Bibliographic Details
Published in:The Journal of neuroscience 2002-09, Vol.22 (18), p.7959-7967
Main Authors: Uveges, Thomas E, Shan, Yuqing, Kramer, Bridget E, Wight, David C, Parysek, Linda M
Format: Article
Language:English
Subjects:
3' Flanking Region - physiology
5' Flanking Region - physiology
Animals
Binding Sites - physiology
Binding, Competitive - drug effects
Binding, Competitive - physiology
Cells, Cultured
DNA Footprinting
Electrophoretic Mobility Shift Assay
Gene Expression - physiology
Genes, Reporter
Humans
Immunohistochemistry
Intermediate Filament Proteins - biosynthesis
Intermediate Filament Proteins - genetics
Introns - physiology
Membrane Glycoproteins
Mice
Mice, Transgenic
Nerve Tissue Proteins - biosynthesis
Nerve Tissue Proteins - genetics
Neurons - cytology
Neurons - metabolism
Oligonucleotides - pharmacology
Organ Specificity - physiology
Peripherins
Rats
Structure-Activity Relationship
Transcription, Genetic - physiology
Transgenes - physiology
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Summary:The "primitive" neurons of the peripheral nervous system (PNS) have the remarkable ability to regenerate new fibers. This regenerative process requires a sequence of gene activation and repression that is poorly understood. One gene that is almost exclusively expressed in neurons of the PNS and is activated after nerve injury is the peripherin intermediate filament gene, but little is known about the genomic elements that control either its restricted expression or its response to nerve injury in adult mice. Previous studies suggested that both 5' flanking sequence and intragenic regions were required for cell type-specific and injury-specific expression. To determine which intragenic regions were critical, mice were generated that expressed peripherin transgenes lacking different introns. Analyses of these mice revealed that deletion of introns 2-8 had no effect on either the cell type-specific or injury-specific expression of the peripherin gene; however, the remaining intron, intron 1, differentially bound Sp1 transcription-related proteins/protein complexes in extracts from peripherin-expressing and nonexpressing tissues. Furthermore, a transgene that lacked intron 1 was not expressed in many neurons that contain endogenous peripherin but was activated after injury. Thus, accurate cell type-specific peripherin gene expression in the PNS depends on elements within intron 1, but other sequences, most likely in the 5'flanking region, are required for activating the peripherin gene in response to nerve injury.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.22-18-07959.2002