scholarly journals Cyclic AMP regulation of the human glycoprotein hormone alpha-subunit gene is mediated by an 18-base-pair element.

1987 ◽  
Vol 84 (8) ◽  
pp. 2198-2202 ◽  
Author(s):  
B. J. Silver ◽  
J. A. Bokar ◽  
J. B. Virgin ◽  
E. A. Vallen ◽  
A. Milsted ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Base Pair ◽  
Alpha Subunit ◽  
Subunit Gene ◽  
Glycoprotein Hormone

Expression of the glycoprotein hormone alpha-subunit gene in the placenta requires a functional cyclic AMP response element, whereas a different cis-acting element mediates pituitary-specific expression

1989 ◽  
Vol 9 (11) ◽  
pp. 5113-5122
Author(s):  
J A Bokar ◽  
R A Keri ◽  
T A Farmerie ◽  
R A Fenstermaker ◽  
B Andersen ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Transgenic Mice ◽  
Regulatory Region ◽  
Alpha Subunit ◽  
Subunit Gene ◽  
Glycoprotein Hormone ◽  
Specific Expression ◽  
Response Element ◽  
Cyclic Amp Response Element ◽  
Choriocarcinoma Cells

The single-copy gene encoding the alpha subunit of glycoprotein hormones is expressed in the pituitaries of all mammals and in the placentas of only primates and horses. We have systematically analyzed the promoter-regulatory elements of the human and bovine alpha-subunit genes to elucidate the molecular mechanisms underlying their divergent patterns of tissue-specific expression. This analysis entailed the use of transient expression assays in a chorionic gonadotropin-secreting human choriocarcinoma cell line, protein-DNA binding assays, and expression of chimeric forms of human or bovine alpha subunit genes in transgenic mice. From the results, we conclude that placental expression of the human alpha-subunit gene requires a functional cyclic AMP response element (CRE) that is present as a tandem repeat in the promoter-regulatory region. In contrast, the promoter-regulatory region of the bovine alpha-subunit gene, as well as of the rat and mouse genes, was found to contain a single CRE homolog that differed from its human counterpart by a single nucleotide. This difference substantially reduced the binding affinity of the bovine CRE homolog for the nuclear protein that bound to the human alpha CRE and thereby rendered the bovine alpha-subunit promoter inactive in human choriocarcinoma cells. However, conversion of the bovine alpha CRE homolog to an authentic alpha CRE restored activity to the bovine alpha-subunit promoter in choriocarcinoma cells. Similarly, a human but not a bovine alpha transgene was expressed in placenta in transgenic mice. Thus, placenta-specific expression of the human alpha-subunit gene may be the consequence of the recent evolution of a functional CRE. Expression of the human alpha transgene in mouse placenta further suggests that evolution of placenta-specific trans-acting factors preceded the appearance of this element. Finally, in contrast to their divergent patterns of placental expression, both the human and bovine alpha-subunit transgenes were expressed in mouse pituitary, indicating differences in the composition of the enhancers required for pituitary- and placenta-specific expression.

Tissue-specific enhancer of the human glycoprotein hormone alpha-subunit gene: dependence on cyclic AMP-inducible elements

1987 ◽  
Vol 7 (11) ◽  
pp. 3994-4002
Author(s):  
A M Delegeane ◽  
L H Ferland ◽  
P L Mellon
Keyword(s):  
Cyclic Amp ◽  
Tissue Specificity ◽  
Specific Activity ◽  
Alpha Subunit ◽  
Unique Element ◽  
Subunit Gene ◽  
Glycoprotein Hormone ◽  
Heterologous Promoter ◽  
Tissue Specific ◽  
Dna Binding Factors

We identified and characterized elements which confer tissue specificity and cyclic AMP (cAMP) responsiveness to the human glycoprotein alpha-subunit gene. An enhancer containing an 18-base-pair repeat conferred cAMP responsiveness in a non-tissue-specific fashion. DNase I protection assays revealed DNA-binding factors that bound to this element in both placental and nonplacental cells. It also enhanced the alpha-subunit promoter in a tissue-specific manner but had a negligible effect on a heterologous promoter. A unique element found upstream of this enhancer had no independent activity but, in combination with the cAMP-responsive enhancer, distinctly increased the tissue-specific activity of both the alpha-subunit promoter and a heterologous promoter. A factor that bound to this upstream element was found in placental but not nonplacental cells. We conclude that this novel element acts, perhaps through a specific trans-acting factor, in concert with a cAMP-responsive enhancer to confer tissue specificity to the alpha-subunit gene.

scholarly journals Expression of the glycoprotein hormone alpha-subunit gene in the placenta requires a functional cyclic AMP response element, whereas a different cis-acting element mediates pituitary-specific expression.

1989 ◽  
Vol 9 (11) ◽  
pp. 5113-5122 ◽  
Author(s):  
J A Bokar ◽  
R A Keri ◽  
T A Farmerie ◽  
R A Fenstermaker ◽  
B Andersen ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Transgenic Mice ◽  
Regulatory Region ◽  
Alpha Subunit ◽  
Subunit Gene ◽  
Glycoprotein Hormone ◽  
Specific Expression ◽  
Response Element ◽  
Cyclic Amp Response Element ◽  
Choriocarcinoma Cells

The single-copy gene encoding the alpha subunit of glycoprotein hormones is expressed in the pituitaries of all mammals and in the placentas of only primates and horses. We have systematically analyzed the promoter-regulatory elements of the human and bovine alpha-subunit genes to elucidate the molecular mechanisms underlying their divergent patterns of tissue-specific expression. This analysis entailed the use of transient expression assays in a chorionic gonadotropin-secreting human choriocarcinoma cell line, protein-DNA binding assays, and expression of chimeric forms of human or bovine alpha subunit genes in transgenic mice. From the results, we conclude that placental expression of the human alpha-subunit gene requires a functional cyclic AMP response element (CRE) that is present as a tandem repeat in the promoter-regulatory region. In contrast, the promoter-regulatory region of the bovine alpha-subunit gene, as well as of the rat and mouse genes, was found to contain a single CRE homolog that differed from its human counterpart by a single nucleotide. This difference substantially reduced the binding affinity of the bovine CRE homolog for the nuclear protein that bound to the human alpha CRE and thereby rendered the bovine alpha-subunit promoter inactive in human choriocarcinoma cells. However, conversion of the bovine alpha CRE homolog to an authentic alpha CRE restored activity to the bovine alpha-subunit promoter in choriocarcinoma cells. Similarly, a human but not a bovine alpha transgene was expressed in placenta in transgenic mice. Thus, placenta-specific expression of the human alpha-subunit gene may be the consequence of the recent evolution of a functional CRE. Expression of the human alpha transgene in mouse placenta further suggests that evolution of placenta-specific trans-acting factors preceded the appearance of this element. Finally, in contrast to their divergent patterns of placental expression, both the human and bovine alpha-subunit transgenes were expressed in mouse pituitary, indicating differences in the composition of the enhancers required for pituitary- and placenta-specific expression.

scholarly journals Tissue-specific enhancer of the human glycoprotein hormone alpha-subunit gene: dependence on cyclic AMP-inducible elements.

1987 ◽  
Vol 7 (11) ◽  
pp. 3994-4002 ◽  
Author(s):  
A M Delegeane ◽  
L H Ferland ◽  
P L Mellon
Keyword(s):  
Cyclic Amp ◽  
Tissue Specificity ◽  
Specific Activity ◽  
Alpha Subunit ◽  
Unique Element ◽  
Subunit Gene ◽  
Glycoprotein Hormone ◽  
Heterologous Promoter ◽  
Tissue Specific ◽  
Dna Binding Factors

We identified and characterized elements which confer tissue specificity and cyclic AMP (cAMP) responsiveness to the human glycoprotein alpha-subunit gene. An enhancer containing an 18-base-pair repeat conferred cAMP responsiveness in a non-tissue-specific fashion. DNase I protection assays revealed DNA-binding factors that bound to this element in both placental and nonplacental cells. It also enhanced the alpha-subunit promoter in a tissue-specific manner but had a negligible effect on a heterologous promoter. A unique element found upstream of this enhancer had no independent activity but, in combination with the cAMP-responsive enhancer, distinctly increased the tissue-specific activity of both the alpha-subunit promoter and a heterologous promoter. A factor that bound to this upstream element was found in placental but not nonplacental cells. We conclude that this novel element acts, perhaps through a specific trans-acting factor, in concert with a cAMP-responsive enhancer to confer tissue specificity to the alpha-subunit gene.

scholarly journals Regulation of Porcine Pituitary Glycoprotein Hormone Alpha Subunit Gene with LIM-Homeobox Transcription Factor Lhx3

2009 ◽  
Vol 55 (4) ◽  
pp. 425-432 ◽  
Author(s):  
Takao SUSA ◽  
Akio ISHIKAWA ◽  
Takako KATO ◽  
Michie NAKAYAMA ◽  
Kousuke KITAHARA ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Alpha Subunit ◽  
Subunit Gene ◽  
Glycoprotein Hormone ◽  
Homeobox Transcription Factor

scholarly journals Role of the Cyclic AMP Response Element Binding Complex and Activation of Mitogen-Activated Protein Kinases in Synergistic Activation of the Glycoprotein Hormone α Subunit Gene by Epidermal Growth Factor and Forskolin

2000 ◽  
Vol 20 (10) ◽  
pp. 3331-3344 ◽  
Author(s):  
Mark S. Roberson ◽  
Makiko Ban ◽  
Tong Zhang ◽  
Jennifer M. Mulvaney
Keyword(s):  
Growth Factor ◽  
Cyclic Amp ◽  
Subunit Gene ◽  
Glycoprotein Hormone ◽  
Α Subunit ◽  
Synergistic Activation ◽  
Mitogen Activated Protein ◽  
A Subunit ◽  
Epidermal Growth ◽  
Combined Actions

ABSTRACT The aim of these studies was to elucidate a role for epidermal growth factor (EGF) signaling in the transcriptional regulation of the glycoprotein hormone α subunit gene, a subunit of chorionic gonadotropin. Studies examined the effects of EGF and the adenylate cyclase activator forskolin on the expression of a transfected α subunit reporter gene in a human choriocarcinoma cell line (JEG3). At maximal doses, administration of EGF resulted in a 50% increase in a subunit reporter activity; forskolin administration induced a fivefold activation; the combined actions of EGF and forskolin resulted in synergistic activation (greater than eightfold) of the α subunit reporter. Mutagenesis studies revealed that the cyclic AMP response elements (CRE) were required and sufficient to mediate EGF-forskolin-induced synergistic activation. The combined actions of EGF and forskolin resulted in potentiated activation of extracellular signal-regulated kinase (ERK) enzyme activity compared with EGF alone. Specific blockade of ERK activation was sufficient to block EGF-forskolin-induced synergistic activation of the α subunit reporter. Pretreatment of JEG3 cells with a p38 mitogen-activated protein kinase inhibitor did not influence activation of the α reporter. However, overexpression of c-Jun N-terminal kinase (JNK)-interacting protein 1 as a dominant interfering molecule abolished the synergistic effects of EGF and forskolin on the α subunit reporter. CRE binding studies suggested that the CRE complex consisted of CRE binding protein and EGF-ERK-dependent recruitment of c-Jun–c-Fos (AP-1) to the CRE. A dominant negative form of c-Fos (A-Fos) that specifically disrupts c-Jun–c-Fos DNA binding inhibited synergistic activation of the α subunit. Thus, synergistic activation of the α subunit gene induced by EGF-forskolin requires the ERK and JNK cascades and the recruitment of AP-1 to the CRE binding complex.

Sign in / Sign up

Export Citation Format

Share Document