AP-2 activation of phenylethanolamine N-methyltransferase gene expression

AP-2 is a vertebrate transcription factor exDNA element consisting of the consensus sequence pressed in neural crest cells and their derivative tissues, 5’-GCCNNNGGC-3’ (Williams and Tjian, 1991a,b). including the adrenal medulla, where epinephrine is proThe 5’ promoter-regulatory regions of many genes duced. AP-2 is shown to stimulate expression of the gene contain similar sequences and hence potential AP-2 encoding the epinephrine biosynthetic enzyme phenylbinding elements. In particular, AP-2 has been shown ethanolamine N-methyltransferase (PNMT). However, to bind to and stimulate expression of several genes stimulation of the PNMT gene by AP-2 requires glucocorticoids and appears to be mediated through the interacexpressed in neural crest-derived tissues, including the tion of AP-2 with activated type II glucocorticoid recephuman insulin-like growth factor binding protein-S tors. Mutation of AP-2 and/or glucocorticoid receptor gene (Duan and Clemmons, 1995), the human proenbinding elemertts within the PNMT promoter disrupts the kephalin gene (Hyman et al., 1989), the rat neuronal ability of AP-2 and glucocorticoids to induce PNMT pronicotinic acetylcholine receptor cr3 subunit gene (Yang moter activity. These findings suggest, in the case of et al., 1995), and the human AP-2 gene itself (Bauer PNMT, that AP-2 stimulates gene expression through a et al., 1994). novel glucocorticoid-dependent mechanism.