Neural specific expression of the m4 muscarinic acetylcholine receptor gene is mediated by a RE1/NRSE-type silencing element - PubMed (original) (raw)
. 1996 Jun 14;271(24):14221-5.
doi: 10.1074/jbc.271.24.14221.
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- PMID: 8662964
- DOI: 10.1074/jbc.271.24.14221
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Neural specific expression of the m4 muscarinic acetylcholine receptor gene is mediated by a RE1/NRSE-type silencing element
I C Wood et al. J Biol Chem. 1996.
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Abstract
Muscarinic receptor genes are members of the G-protein receptor superfamily that, with the inclusion of the odorant receptors, is believed to contain over a thousand members. Each member of this superfamily, which has been studied to date, appears to have a distinct pattern of expression, but little work has been done on the regulation of these complex expression patterns. We have recently isolated the rat m4 muscarinic receptor gene and identified a genomic 1520-nucleotide sequence that appeared capable of directing cell-specific expression (Wood, I. C., Roopra. A., Harrington, C., and Buckley, N. J. (1995) J. Biol. Chem. 270, 30933-30940). In the present study we have constructed a set of deletion promoter constructs to more closely define the DNA elements that are responsible for m4 gene expression. We have found that deletion of a RE1/NRSE silencer element between nucleotides -574 and -550, similar to that found in other neural specific genes, results in activation of reporter expression in non-m4-expressing cells. Gel mobility shift analysis has shown that a protein present in nonexpressing cells is capable of binding to this element and is probably the recently identified neural silencer, REST/NRSF. Of the constitutively active proximal promoter only a tandem Sp-1 site appears to recruit DNA binding proteins that are present in all cells tested. This represents the first report documenting the role of this silencer in regulating expression of a member of the G-protein receptor family.
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