Abstract
Pregnancy‐specific glycoproteins (PSGs) are fetal proteins secreted by the placenta during pregnancy. The PSG level in maternal serum is an indicator of risk for pregnancy complications. However, little is known about the molecular mechanisms underlying PSG gene expression. Recently, the importance of epigenetic regulation of placental genes has been emphasized in the study of developmental defects and placental disease. In this study, the role of the CCCTC‐binding factor (CTCF) in regulation of PSG expression was investigated to better understand the epigenetic regulatory mechanisms of the PSG genes. Inhibition of CTCF expression disturbed transcription of several PSG genes: PSG1, PSG2, PSG4, PSG5, PSG8, and PSG9 were upregulated and PSG6 and PSG11 were downregulated. These transcriptional changes were correlated with decreased CTCF binding and changes in histone modification at the PSG promoters. Our data demonstrate that CTCF is a potential mediator in the regulation of PSG gene expression.
Highlights
Pregnancy-specific glycoproteins (PSGs) are fetal proteins secreted by the placenta during pregnancy
FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies
In the enlarged genomic map, three strong CCCTC-binding factor (CTCF) binding peaks are common to all PSG genes, except PSG3 and PSG8, two of which are in the upstream region of each gene (Fig. 1B)
Summary
Pregnancy-specific glycoproteins (PSGs) are fetal proteins secreted by the placenta during pregnancy. Several case–control studies have shown that low levels of PSG are associated with complicated pregnancy outcomes such as intrauterine growth retardation (IUGR), preterm labor, and pre-eclampsia (PE) [7,8,9]. These reports imply the pivotal roles of PSG in successful pregnancy outcomes; the molecular mechanism underlying the regulation of PSG gene expression is not well understood. Abbreviations CEA, carcinoembryonic antigen; ChIP, chromatin immunoprecipitation; CTCF, CCCTC-binding factor; H1-hESC, H1 human embryonic stem cell; HUVEC, human umbilical vein endothelial cell; HVMF, human villous mesenchymal fibroblast; IUGR, intrauterine growth retardation; PE, pre-eclampsia; PSGs, pregnancy-specific glycoproteins; UCSC, University of California Santa Cruz. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies
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