Multiple promoters drive tissue-specific expression of the human M muscarinic acetylcholine receptor gene
Language English Country Great Britain, England Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
15379890
DOI
10.1111/j.1471-4159.2004.02694.x
PII: JNC2694
Knihovny.cz E-resources
- MeSH
- Cell Line MeSH
- Chromatin metabolism MeSH
- DNA-Binding Proteins metabolism MeSH
- Exons MeSH
- Immunoprecipitation methods MeSH
- Cloning, Molecular methods MeSH
- Rats MeSH
- Humans MeSH
- Luciferases metabolism MeSH
- RNA, Messenger genetics MeSH
- Molecular Sequence Data MeSH
- Mutagenesis physiology MeSH
- Myoblasts MeSH
- Mice MeSH
- Neuroblastoma MeSH
- Organ Specificity MeSH
- Reverse Transcriptase Polymerase Chain Reaction methods MeSH
- Promoter Regions, Genetic physiology MeSH
- TATA-Box Binding Protein metabolism MeSH
- Receptor, Muscarinic M2 genetics metabolism MeSH
- Gene Expression Regulation physiology MeSH
- Genes, Reporter physiology MeSH
- Electrophoretic Mobility Shift Assay methods MeSH
- Amino Acid Sequence MeSH
- Sequence Alignment methods MeSH
- GATA4 Transcription Factor MeSH
- Transcription Factors metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Chromatin MeSH
- DNA-Binding Proteins MeSH
- Luciferases MeSH
- RNA, Messenger MeSH
- TATA-Box Binding Protein MeSH
- Receptor, Muscarinic M2 MeSH
- GATA4 Transcription Factor MeSH
- Transcription Factors MeSH
Despite the wealth of information on the functional and pharmacological properties of the M2 muscarinic receptor, we know relatively little of structure and regulation of the M2 receptor gene. Here, we describe the organisation of the human M2 gene and its promoters. Four exons are present in the 5' untranslated region of the human M2 mRNA distributed over 146 kb on chromosome 7 which produce eight different splice variants in the IMR-32 neuroblastoma cell line. The unexpectedly large size of this gene indicates that transcription initiates much further upstream of the coding region than earlier studies had indicated. We present evidence that there are three distinct human M2 promoters. Analysis of endogenous transcripts revealed that promoter 2 is preferentially used in neuroblastoma cells, whereas promoter 1 in cardiac cells. All promoters are highly conserved across human, mouse, rat and pig. They contain multiple start sites and none possess a TATA-box. In addition, we describe another M2 promoter that is specific for rat. We show that GATA-4 transcription factor binds to two sites within the regulatory regions of the M2 gene using reporter gene assays, electromobility shift assays and mutational analysis.
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GENBANK
AY456125, AY456126, AY456127, AY456128, AY456129, AY571965
