Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
41
pubmed:dateCreated
1994-11-17
pubmed:databankReference
pubmed:abstractText
Mutations affecting the peripheral myelin protein-22 (PMP22) gene have been shown to be associated with inherited peripheral neuropathies. To provide the molecular basis for the analysis of such mutations, we have cloned and characterized the human PMP22 gene. It spans approximately 40 kilobases and contains four coding exons. Detailed analysis of its 5'-flanking region suggested the presence of two alternatively transcribed, but untranslated exons. Mapping of separate PMP22 mRNA transcription initiation sites to each of these exons indicates that PMP22 expression is regulated by two alternatively used promoters. In support of this hypothesis, both putative promoter sequences demonstrated the ability to drive expression of reporter genes in transfection experiments. Furthermore, the structures of the 5'-portions of the PMP22 genes appear to be identical in rat and human, supporting the biological significance of the observed arrangement of regulatory regions. The relative expression of the alternative PMP22 transcripts is tissue-specific, and high levels of the exon 1A-containing transcript are tightly coupled to myelin formation. In contrast, exon 1B-containing transcripts are predominant in non-neural tissues and in growth-arrested primary fibroblasts. Interestingly, although a strong upregulation of PMP22 mRNA was observed in cultured Schwann cells in the presence of the adenylate cyclase activator forskolin under various culture conditions, the regulation of the different PMP22 mRNA species did not mimic the regulation that occurs during myelin formation in vivo. The observed regulation of the PMP22 gene by a complex molecular mechanism is consistent with the proposed dual role of PMP22 in neural and non-neural tissue.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25795-808
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:7929285-Alternative Splicing, pubmed-meshheading:7929285-Animals, pubmed-meshheading:7929285-Base Sequence, pubmed-meshheading:7929285-Cells, Cultured, pubmed-meshheading:7929285-Cloning, Molecular, pubmed-meshheading:7929285-Cricetinae, pubmed-meshheading:7929285-Fibroblasts, pubmed-meshheading:7929285-Forskolin, pubmed-meshheading:7929285-Genome, Human, pubmed-meshheading:7929285-Hereditary Sensory and Motor Neuropathy, pubmed-meshheading:7929285-Humans, pubmed-meshheading:7929285-Molecular Sequence Data, pubmed-meshheading:7929285-Myelin Proteins, pubmed-meshheading:7929285-Nerve Regeneration, pubmed-meshheading:7929285-Promoter Regions, Genetic, pubmed-meshheading:7929285-RNA, Messenger, pubmed-meshheading:7929285-Rats, pubmed-meshheading:7929285-Schwann Cells, pubmed-meshheading:7929285-Sciatic Nerve, pubmed-meshheading:7929285-Sequence Analysis, DNA, pubmed-meshheading:7929285-Species Specificity, pubmed-meshheading:7929285-Tissue Distribution, pubmed-meshheading:7929285-Transcription, Genetic
pubmed:year
1994
pubmed:articleTitle
Regulation of tissue-specific expression of alternative peripheral myelin protein-22 (PMP22) gene transcripts by two promoters.
pubmed:affiliation
Department of Cell Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, Zürich.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't