Elements of the glucocorticoid and retinoic acid response units are involved in cAMP-mediated expression of the PEPCK gene.
Although many genes are regulated by the concerted action of several hormones, hormonal signaling to gene promoters has generally been studied one hormone at a time. The phosphoenolpyruvate carboxykinase (PEPCK) gene is a case in point. Transcription of this gene is induced by glucagon (acting by the second messenger, cAMP), glucocorticoids, and retinoic acid, and it is dominantly repressed by insulin. These hormonal responses require the presence of different hormone response units (HRUs), which consist of constellations of DNA elements and associated transcription factors. These include the glucocorticoid response unit (GRU), cAMP response unit (CRU), retinoic acid response unit (RARU), and the insulin response unit. HRUs are known to have functional overlap. In particular, the cAMP response element of the CRU is also a component of the GRU. The purpose of this study was to determine whether known GRU or RARU elements or transcription factors function as components of the CRU. We show here that the glucocorticoid accessory factor binding site 1 and glucocorticoid accessory factor binding site 3 elements, which are components of both the GRU and RARU, are an important part of the CRU. Furthermore, we find that the transcription factor, chicken ovalbumin upstream promoter-transcription factor, and two coactivators, cAMP response element-binding protein-binding protein and steroid receptor coactivator-1, participate in both the cAMP and glucocorticoid responses. This provides a further illustration of how the PEPCK gene promoter integrates different hormone responses through overlapping HRUs that utilize some of the same transcription factors and coactivators.
Waltner-Law
Mary
M
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615, USA.
Duong
David T
DT
Daniels
Marc C
MC
Herzog
Birger
B
Wang
Xiaohui L
XL
Prasad
Ratna
R
Granner
Daryl K
DK
D051836:COUP Transcription Factors; D002352:Carrier Proteins / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D005938:Glucocorticoids / Q000494:pharmacology*; D051548:Histone Acetyltransferases; D006801:Humans; D056920:Nuclear Receptor Coactivator 1; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011987:Receptors, Steroid; D020218:Response Elements / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D051836:COUP Transcription Factors; D002352:Carrier Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D011987:Receptors, Steroid; D014157:Transcription Factors; C020723:citrate-binding transport protein; D014212:Tretinoin; D000242:Cyclic AMP; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; D017868:Cyclic AMP-Dependent Protein Kinases; D010729:Phosphoenolpyruvate Carboxykinase (GTP)