Regulation of tissue-specific expression of alternative peripheral myelin protein-22 (PMP22) gene transcripts by two promoters

Journal Article · Thu Sep 01 04:00:00 UTC 1994 · American Journal of Human Genetics

OSTI ID:133858

Patel, P I; Schoener-Scott, R; Lupski, J R ^[1]

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1. Baylor College of Medicine, Houston, TX (United States); and others

Mutations affecting the peripheral myelin protein-22 (PMP22) gene have been shown to be associated with inherited peripheral neuropathies. We have cloned and characterized the human PMP22 gene which spans approximately 40 kilobases and contains four coding exons. Towards developing gene therapy regimens for the associated peripheral neuropathies, we have initiated detailed analysis of the 5{prime} flanking region of the PMP22 gene and identified 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. Both putative promoter sequences demonstrated the ability to drive expression of reporter genes in transfection experiments. Furthermore, the structure of the 5{prime} portion of the PMP22 gene appears 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. The observed regulation of the PMP22 by a complex molecular mechanism is consistent with the proposed dual role of PMP22 in neural and non-neural tissue.

• OSTI ID: 133858
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
COMPARATIVE EVALUATIONS
DNA-CLONING
GENE MUTATIONS
GENE REGULATION
GENE REPRESSORS
GENES
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN POPULATIONS
MESSENGER-RNA
MYELIN
NERVOUS SYSTEM DISEASES
PROTEINS
RATS
STRUCTURE-ACTIVITY RELATIONSHIPS
TISSUE DISTRIBUTION
TRANSCRIPTION