Glucocorticoid-dependent action of neural crest factor AP-2: stimulation of phenylethanolamine N-methyltransferase gene expression.
AP-2 is a vertebrate transcription factor expressed in neural crest cells and their derivative tissues, including the adrenal medulla, where epinephrine is produced. AP-2 is shown to stimulate expression of the gene encoding the epinephrine biosynthetic enzyme phenylethanolamine N-methyltransferase (PNMT). However, stimulation of the PNMT gene by AP-2 requires glucocorticoids and appears to be mediated through the interaction of AP-2 with activated type II glucocorticoid receptors. Mutation of AP-2 and/or glucocorticoid receptor binding elements within the PNMT promoter disrupts the ability of AP-2 and glucocorticoids to induce PNMT promoter activity. These findings suggest, in the case of PNMT, that AP-2 stimulates gene expression through a novel glucocorticoid-dependent mechanism.
Ebert
S N
SN
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, California 94305-5485, USA.
Ficklin
M B
MB
Her
S
S
Siddall
B J
BJ
Bell
R A
RA
Ganguly
K
K
Morita
K
K
Wong
D L
DL
D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D019439:Chromaffin Cells / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D005822:Genetic Vectors; D005938:Glucocorticoids / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D010625:Phenylethanolamine N-Methyltransferase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D010625:Phenylethanolamine N-Methyltransferase