Different combinations of regulatory elements may explain why placenta-specific expression of the glycoprotein hormone alpha-subunit gene occurs only in primates and horses.
Abstract: Expression of the glycoprotein hormone alpha-subunit gene occurs in the pituitary of all mammals but in placenta of only primates and horses. In humans, two different elements, termed upstream regulatory element (URE) and cAMP response element (CRE), are required for placenta-specific expression of the alpha-subunit gene. The URE binds a protein unique to placenta whereas the CRE binds a ubiquitous protein. Comparative analysis of the promoter-regulatory region of the alpha-subunit gene from a number of mammals indicates that a functional URE has been retained and suggests the potential for placenta-specific expression. Indirect evidence also indicates that the URE-binding protein has been conserved, even in placenta from mammals that fail to express the alpha-subunit gene. Lack of expression of the alpha-subunit gene in placenta of rodents and cattle can be traced to a single nucleotide change that renders the CRE-like sequence of these genes incapable of binding the protein that confers responsiveness to cAMP. In contrast, although expression of the alpha-subunit gene occurs in horse placenta, the promoter-regulatory region lacks a functional CRE but appears to retain a functional URE. This suggests that either a different accessory element and cognate protein interacts with the horse URE to provide placenta-specific expression or that a completely different set of regulatory elements is required for placenta-specific expression in horses.
Publication Date: 1991-02-01 PubMed ID: 1706947DOI: 10.1095/biolreprod44.2.231Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
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Summary
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This research article explores why the expression of the glycoprotein hormone alpha-subunit gene, which generally takes place in the pituitary of all mammals, is specifically observed in the placenta of only primates and horses.
Introduction
Certain mammals, particularly primates and horses, exhibit a unique trait where the glycoprotein hormone alpha-subunit gene (α-subunit gene) is expressed in the placenta. While the α-subunit gene is typically expressed in the pituitary of all mammals, this placenta-specific expression is exclusive to these animal groups. The study aims at understanding the reason for this selective gene expression.
Regulatory Elements and their Roles
- Two regulatory elements, namely the Upstream Regulatory Element (URE) and the cAMP Response Element (CRE), join forces in humans for placenta-specific expression of the α-subunit gene.
- The URE plays a crucial part as it binds a protein that is exclusive to the placenta.
- Although the CRE, on the other hand, binds a protein that is ubiquitously present, it nevertheless contributes to this specific gene expression.
Functional differences among mammals
- While the α-subunit gene is expressed in the horse’s placenta, the promoter-regulatory region lacks a functional CRE but seems to retain a functional URE.
- This may suggest that a different accessory element and related protein interact with the horse URE for placenta-specific expression or perhaps an altogether different set of regulatory elements is required for the process in horses.
- On the contrary, rodents and cattle, despite possessing the URE-binding protein, do not express the α-subunit gene in their placentae. This is traced to a single nucleotide change, which makes the CRE-like sequence of these genes incapable of binding the protein responsible for making the genes responsive to cAMP.
Concluding Remarks
By examining the alpha-subunit gene from various mammals, the study suggests that a functional URE has been retained, implying the possibility of placenta-specific gene expression. Indirect evidence also points towards the conservation of the URE-binding protein across species, further reinforcing the critical role these regulatory elements play in placenta-specific gene expression in certain mammals.
Cite This Article
APA
Nilson JH, Bokar JA, Clay CM, Farmerie TA, Fenstermaker RA, Hamernik DL, Keri RA.
(1991).
Different combinations of regulatory elements may explain why placenta-specific expression of the glycoprotein hormone alpha-subunit gene occurs only in primates and horses.
Biol Reprod, 44(2), 231-237.
https://doi.org/10.1095/biolreprod44.2.231 Publication
Researcher Affiliations
- Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106.
MeSH Terms
- Animals
- Base Sequence
- DNA / genetics
- Female
- Genes, Regulator
- Glycoprotein Hormones, alpha Subunit / genetics
- Horses
- Humans
- Molecular Sequence Data
- Placenta / metabolism
- Pregnancy
- Primates
Grant Funding
- AM-28559 / NIADDK NIH HHS
- DK-0731 / NIDDK NIH HHS
- HD07138-03 / NICHD NIH HHS
Citations
This article has been cited 5 times.- Xie H, Cherrington BD, Meadows JD, Witham EA, Mellon PL. Msx1 homeodomain protein represses the αGSU and GnRH receptor genes during gonadotrope development. Mol Endocrinol 2013 Mar;27(3):422-36.
- Gupta R, Ezashi T, Roberts RM. Squelching of ETS2 transactivation by POU5F1 silences the human chorionic gonadotropin CGA subunit gene in human choriocarcinoma and embryonic stem cells. Mol Endocrinol 2012 May;26(5):859-72.
- Pfenning AR, Schwartz R, Barth AL. A comparative genomics approach to identifying the plasticity transcriptome. BMC Neurosci 2007 Mar 13;8:20.
- Roberson MS, Ban M, Zhang T, Mulvaney JM. Role of the cyclic AMP response element binding complex and activation of mitogen-activated protein kinases in synergistic activation of the glycoprotein hormone alpha subunit gene by epidermal growth factor and forskolin. Mol Cell Biol 2000 May;20(10):3331-44.
- Kamat A, Graves KH, Smith ME, Richardson JA, Mendelson CR. A 500-bp region, approximately 40 kb upstream of the human CYP19 (aromatase) gene, mediates placenta-specific expression in transgenic mice. Proc Natl Acad Sci U S A 1999 Apr 13;96(8):4575-80.
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