The Journal of Neuroscience, September 15, 2002, 22(18):7959-7967
Intron 1 Is Required for Cell Type-Specific, But Not
Injury-Responsive, Peripherin Gene Expression
Thomas E.
Uveges1,
Yuqing
Shan1,
Bridget E.
Kramer1,
David C.
Wight2, and
Linda M.
Parysek1
1 Department of Cell Biology, Neurobiology and Anatomy,
University of Cincinnati, Cincinnati, Ohio 45267-0521, and
2 Ohio University, Edison Biotechnology Institute, Konneker
Research Laboratories, Ohio University, Athens, Ohio 45701-2979
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.
Key words:
peripherin; gene regulation; injury-induced expression; cell type-specific expression; intermediate filament; intron; nerve
injury; Sp1; NFI
Copyright © 2002 Society for Neuroscience 0270-6474/02/22187959-09$05.00/0