Document Detail


Structure and transcription of the human m3 muscarinic receptor gene.
MedLine Citation:
PMID:  11867338     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have isolated and characterized the human m3 muscarinic receptor gene and its promoter. Using 5' rapid amplification of cDNA ends (RACE), internal polymerase chain reaction (PCR), and homology searching to identify EST clones, we determined that the cDNA encoding the m3 receptor comprises 4,559 bp in 8 exons, which are alternatively spliced to exclude exons 2, 4, 6, and/or 7; the receptor coding sequence occurs within exon 8. Analysis of P1 artificial chromosome (PAC) and bacterial artificial chromosome (BAC) clones and of PCR- amplified genomic DNA, and homology searching of human chromosome 1 sequence provided from the Sanger Centre (Hinxton, Cambridge, UK) revealed that the m3 muscarinic receptor gene spans at least 285 kb. A promoter fragment containing bp -1240 to +101 (relative to the most 5' transcription start site) exhibited considerable transcriptional activity during transient transfection in cultured subconfluent, serum-fed canine tracheal myocytes, and 5' deletion analysis of promoter function revealed the presence of positive transcriptional regulatory elements between bp -526 and -269. Sequence analysis disclosed three potential AP-2 binding sites in this region; five more AP-2 consensus binding motifs occur between bp -269 and +101. Cotransfection with a plasmid expressing human AP-2alpha substantially increased transcription from m3 receptor promoter constructs containing 526 or 269 bp of 5' flanking DNA. Furthermore, m3 receptor promoter activity was enhanced by long-term serum deprivation of canine tracheal myocytes, a treatment that is known to increase AP-2 transcription-promoting activity in these cells. Together, these data suggest that expression of the human m3 muscarinic receptor gene is regulated in part by AP-2 in airway smooth muscle.
Authors:
Sean M Forsythe; Paul C Kogut; John F McConville; Yiping Fu; Joel A McCauley; Andrew J Halayko; Hong Wei Liu; Allen Kao; Darren J Fernandes; Shashi Bellam; Elaine Fuchs; Satrajit Sinha; Graeme I Bell; Blanca Camoretti-Mercado; Julian Solway
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  26     ISSN:  1044-1549     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2002 Mar 
Date Detail:
Created Date:  2002-02-27     Completed Date:  2002-03-29     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  298-305     Citation Subset:  IM    
Affiliation:
Section of Pulmonary and Critical Care Medicine, Department of Medicine, Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AF331832;  AF331833;  AF331834;  AF331835;  AF331836;  AF331837;  AF331838
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MeSH Terms
Descriptor/Qualifier:
Alternative Splicing
Animals
Base Sequence
Cells, Cultured
DNA, Complementary / analysis,  genetics
Dogs
Exons / genetics
Genome, Human*
Humans
Molecular Sequence Data
Promoter Regions, Genetic*
Receptor, Muscarinic M3
Receptors, Muscarinic / genetics*
Sequence Alignment
Sequence Analysis, DNA
Transcription, Genetic
Grant Support
ID/Acronym/Agency:
HL07605/HL/NHLBI NIH HHS; HL56399/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Complementary; 0/Receptor, Muscarinic M3; 0/Receptors, Muscarinic
Comments/Corrections
Comment In:
Am J Respir Cell Mol Biol. 2002 Mar;26(3):269-72   [PMID:  11867333 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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