Human and mouse studies over the past several years have identified novel promoters and exons within GNAS, thereby unveiling the previously unrecognized complexity of this gene locus. The sense strand comprises at least three promoters besides the promoter driving the expression of the aforementioned Gsα variants (Fig. 2). In addition, there is at least one promoter that shows activity on the antisense strand. All of the recently described promoters are located within CpG islands that show differential, parent-of-origin specific methylation. Therefore, the GNAS locus harbors a total of four distinct DMRs. Consistent with the differential methylation of its promoter, each of the additional GNAS product shows an imprinted expression profile in nearly all tissues investigated in that regard.
