GPCR promoter architecture

Promoters can be divided into at least three classes depending upon the presence of certain core motifs. Many genes possess a TATAbox 25-30 bp upstream of the transcription initiation site (TIS)—such genes normally have a singular TIS. Other genes lack a TATA box but have an initiator sequence spanning multiple start sites. Another class of genes contain neither of these motifs but are characterized by GC-richness and multiple start sites. All these architectures have been described for GPCR promoters, although the majority are of the latter category, TATA-less, GC-rich with multiple start sites.

Some GPCR genes contain multiple mixed promoters such as the rat a-1B adrenergic receptor that contains three promoters. The first lacks any consensus motif, the second is GC-rich and TATA-less (major) and the third is a TATA-containing promoter (Gao and Kunos 1994). There is little obvious contribution that the promoter architecture of a gene can tell us about its transcriptional regulation. The early notion that TATA-less GC-rich genes encode constitutively active house-keeping proteins is long overturned—not least by studies of GPCR promoters. Numerous studies have identified regulatory elements in several GPCR genes and, in a minority of studies, identification of cis regulatory elements or domains has been used to identify potential cognate transcription factors. In general, these sites and factors have been identified on the basis of transient reporter gene analysis and few seem to account for cell specific expression in this type of assay. Some of these details are catalogued in Table 2.1.

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