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 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.
Uveges
Thomas E
TE
Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati, Cincinnati, Ohio 45267-0521, USA.
Shan
Yuqing
Y
Kramer
Bridget E
BE
Wight
David C
DC
Parysek
Linda M
LM
D024509:3' Flanking Region / Q000502:physiology; D024506:5' Flanking Region / Q000502:physiology; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018983:DNA Footprinting; D024202:Electrophoretic Mobility Shift Assay; D015870:Gene Expression / Q000502:physiology*; D017930:Genes, Reporter; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000096:biosynthesis* / Q000235:genetics*; D007438:Introns / Q000502:physiology*; D008562:Membrane Glycoproteins; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009841:Oligonucleotides / Q000494:pharmacology; D009928:Organ Specificity / Q000502:physiology; D064531:Peripherins; D051381:Rats; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000502:physiology; D019076:Transgenes / Q000502:physiology
D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009841:Oligonucleotides; C578994:PRPH protein, human; D064531:Peripherins