Gene and Promoter Structures of the Dopamine Receptors

The dopamine receptors have been classified into two groups, the D1like and D2-like dopamine receptors, respectively, based on molecular biology and pharmacological studies. The D1-like dopamine receptors comprise the D1 and D5 dopamine receptors and the D2-like dopamine receptors include the D2, D3 and D4 dopamine receptors. The gene structures of these two classes of receptors are dissimilar with respect to the organization of their coding and regulatory regions. First, the D2-like dopamine receptor genes have revealed the presence of coding exons separated by introns whereas the D1-like dopamine receptor genes consist of a single exon and thus are intronless. Second, examination of the 5regulatory regions reveals the presence of non-coding exon(s) several kilobases upstream from their coding exons in the D2 and D3 dopamine receptor genes, while regulatory regions of the D1-like dopamine receptor genes have only one noncoding exon that is separated by a small intron from the coding exon. However, in general, characterization of the 5-flanking regions of the dopamine receptor genes demonstrates that they lack TATA boxes or CCAAT boxes, are GC rich and have several consensus binding sites for the transcription factor Sp1. The regulatory region of the D2 dopamine receptor gene is similar to that in the D3 dopamine receptor gene as they both contain an initiator-like element suggesting transcription initiation from this position and are under strong negative regulation in mammalian cell cultures. Furthermore, amongst the dopamine receptor genes, the 5-flanking regions of the D3 and D5 dopamine receptors have much lower GC content than those in the D1, D2 and D4 dopamine receptor genes. Nevertheless, overall, the promoter regions of all the dopamine receptor genes are regulated in a cell-specific manner, including the additional promoter of the D1 dopamine receptor gene located within intron 1. There are several studies that have identified transcription factors (DNA binding proteins) that regulate the dopamine receptor genes, U.M. D’Souza (B) MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King’s College, London, UK e-mail: ursula.d’[email protected] 23 K.A. Neve (ed.), The Dopamine Receptors, 2nd Edition, The Receptors, DOI 10.1007/978-1-60327-333-6_2, C © Humana Press, a part of Springer Science+Business Media, LLC 2010