Role of the Transcription Factor C/EBPβ in Expression of a Rat Pregnancy-Specific Glycoprotein Gene

Abstract

Pregnancy-specific glycoproteins (PSGs), which are the major placental proteins, and the carcinoembryonic antigens comprise a subfamily within the immunoglobulin superfamily. To understand the molecular mechanisms underlying the control of PSG expression, we characterized the promoter elements of a rodent PSG gene, rnCGM3, and showed that DNA elements at nucleotides -326 to -185 (PI) relative to the translation start site of rnCGM3 function as a promoter. The rnCGM3 PI promoter contains two placental factor binding sites, PISI and PISII. Both are transcription activation elements. In the present report, we screened a placental expression cDNA library with a rnCGM3-PISII probe (nucleotides -263 to -233) encompassing two overlapping palindromes (TGTTGCTCAACATGTTG) and demonstrated that the PISII-binding factor is C/EBP beta, a leucine zipper family of transcription factor. Gel mobility-shift and transient expression analyses showed that C/EBP beta and C/EBP isoforms, C/EBP alpha and C/EBP delta, bind to the PISII element and trans-activate rnCGM3 gene expression. Deletion of PISII from the rnCGM3 PI promoter greatly reduced the basal as well as the C/EBP-activated rnCGM3 expression. Gel supershift assays demonstrated that C/EBP beta is the placental isoform that binds to the PISII site rnCGM3. Moreover, C/EBP beta is expressed in high levels in the placenta, ovary, liver, lung, heart, and spleen, in contrast to C/EBP alpha, which is expressed primarily in the liver and only low levels in the placenta. Our results demonstrate that C/EBP beta is one of the transcription factors that positively regulate rnCGM3 expression during pregnancy.

CCAAT-enhancer-binding Protein β (C/EBPβ) and Downstream Human Placental Growth Hormone Genes Are Targets for Dysregulation in Pregnancies Complicated by Maternal Obesity

“…C/EBP␤ production in placenta is localized to syncytiotrophoblasts in both human and non-human primates, which is consistent with a role in CS/GH-V gene regulation (67). Remarkably, the villous cytotrophoblasts are negative for C/EBP␤ immunostaining at all stages of gestation (37,68,69), and as the syncytial layer derives from the fusion of cytotrophoblasts, this might predict a role for C/EBP␤ in cytotrophoblast differentiation into syncytiotrophoblast (70).…”

Expression pattern of the CCAAT/enhancer-binding proteins C/EBP-?, C/EBP-? and C/EBP-? in the human placenta

“…Furthermore, C/EBP factors (and especially C/EBP-b) have been shown to stimulate promoter activity of pregnancy-specific glycoproteins, proteins primarily expressed in the placenta, which become the major glycoproteins at term [4]. This stimulation was later shown by Notch to be enhanced [5].…”

The C/EBPβ transcription factor regulates epithelial cell proliferation and differentiation in the mammary gland

“…), the placenta (Chen et al 1995), and possibly the pituitary (Wegner et al 1992), which are important for the development of the lactating mammary gland. Thus, we cannot rule out that other hormonal defects of the mutants are in part responsible for the impaired development of the mammary gland.…”