Work

Subtle differences in human pregnancy-specific glycoprotein gene promoters allow for differential expression.

Year: 1994

Type: article

Abstract: Eleven pregnancy-specific glycoprotein (PSG) genes reside on human chromosome 19.The sequence of these genes is extremely similar and that similarity extends to their putative control regions.However, the expression pattern of each PSG gene differs in the placenta, the primary site of PSG synthesis.To understand the molecular mechanisms underlying differential PSG expression, we characterized promoter elements of six PSG genes.We have shown previously that nucleotides -172 to -34 with respect to the translation start site constitute a minimal promoter in the PSG12 gene (class 1).W e now show that PSG1-I and PSG3 are also members of class 1 genes.In contrast, only nucleotides -172 to -80 are necessary for promoter activity in PSG5, PSGG, and PSGll genes (class 2).Class 2 genes contain a perfect Spl recognition sequence (CCCCGCCC) at nucleotides -148 to -141 which is necessary for promoter activity.Placental cell extracts formed three protein-DNA complexes with nucleotides -172 to -80 of all six PSG genes.One of the components of these complexes is an Spl-like molecule.We have previously reported activator sequences within nucleotides -83 to -34 in PSG12.W e now show that a BO-kDa protein binds to this region of PSGl2, and the resultant complex can be supershifted by a monoclonal antibody to PEA3.The human placenta is the site of synthesis of a number of pregnancy-specific proteins, including the group known prosaically as pregnancy-specific glycoproteins (PSGs)' (1-3).The PSGs are the most abundant placental proteins in maternal serum at term where they are found at concentrations of 200-400 pglml (3, 4).Although the function of PSG proteins is unknown, the high concentrations are necessary for successful pregnancies.Low concentrations of PSGs are associated with threatened abortions (5, 61, intrauterine growth retardation (7), and fetal hypoxia (8).Additionally, serum levels of PSGs are elevated in patients with hydatidiform mole, invasive mole, and choriocarcinoma (9, 10).Aberrant expression of PSGs have also been associated with neoplastic transformations (11).Analysis of cDNAs and genes that encode human PSGs revealed the existence of 11 similar, yet distinct, PSG genes which mapped to chromosome 19q (12-22).The PSGs are highly related to the carcinoembryonic antigen (CEA) gene * The costs of publication of this article were defrayed in part by the payment of page charges.This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C.Section 1734 solely to indicate this fact. to the GenBankm/EMBL Data Bank with accession number(s) U09003The nucleotide sequence(s) reported in this paper has been submitted (PSG5gb.se)and UO9004 (psg3gb).

Source: Journal of Biological Chemistry

DOI: 10.1016/s0021-9258(17)32534-6

Authors: M.E. Chamberlin, K.J. Lei, J.Y. Chou

Institutions: National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development

Language: English

Topic: Reproductive System and Pregnancy

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430