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Papers In Press, published online ahead of print December 12, 2001
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante 03550
Corresponding Author: manuel.criado{at}umh.es
The
J. Biol. Chem, 10.1074/jbc.M110454200
Submitted on October 31, 2001
Revised on December 11, 2001
Accepted on December 12, 2001
Transcription factors NF-Y and Sp1 are important determinants of the promoter activity of the bovine and human neuronal nicotinic receptor beta4 subunit genes
4 subunit is a component of the neuronal nicotinic acetylcholine receptors which control catecholamine secretion in bovine adrenomedullary chromaffin cells. The promoter of the gene coding for this subunit was characterized. A proximal region (from –99 to -64) was responsible for the transcriptional activity observed in chromaffin, C2C12 and COS cells. Within this region two cis-acting elements that bind transcription factors Sp1 and NF-Y were identified. Mutagenesis of the two elements indicated that they cooperate for the basal transcription activity of the promoter. The human 4 promoter, that was also characterized, shared structural and functional homologies with the bovine promoter. Thus, two adjacent binding elements for Sp1 and NF-Y were detected. Whereas the Sp1 site was an important determinant of the promoter activity, the NF-Y site may have cell-specific effects. Given that these promoters showed no structural or functional homology with the previously characterized rat 4 subunit promoter (Bigger et al., J. Biol. Chem. 271:32842, 1996) except for the involvement of an Sp1 binding element, we propose that constitutive expression of the 4 subunit gene in these three close species may be controlled by the general transcription factor Sp1. Nevertheless, other components could determine species-specific 4 subunit expression.
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