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

Abstract

The human trophoblast has the capacity to invade maternal tissue in a controlled fashion and to produce a wide range of hormones. The transcription factors belonging to the CCAAT/enhancer-binding protein (C/EBP) family are regulators of intracellular processes and mediators of hormone action. C/EBP binding sites have been described in the promoters of several placenta-expressed target genes. In the present study, we used immunohistochemistry and Western-blot analysis to investigate the expression pattern of the three most important members of this family, C/EBP-alpha, -beta, and -delta, in the normal human placenta as well as in isolated trophoblast cell populations. We found C/EBP-alpha and C/EBP-beta expression in the villous syncytiotrophophoblast (ST) and the extravillous (intermediate) trophoblast (EVT), but it was absent from the villous cytotrophoblast (CT). Interestingly, expression of C/EBP-beta continued to be very strong up to the third trimester of pregnancy, especially in the ST. C/EBP-delta showed overall lower expression levels, stronger only in the EVT, while CT/ST showed very low/negative expression. These data show for the first time the expression pattern and tissue localization of C/EBP factors in the human placenta, indicating that these factors (especially C/EBP-beta) may play important roles in the regulation of placenta-specific genes and processes.

Identification of functional CCAAT/enhancer-binding protein and Ets protein binding sites in the human chorionic somatomammotropin enhancer sequences

“…Ets and C/EBP proteins are expressed in placenta and have been shown to interact in a variety of tissues and gene contexts, including placental and pituitary gene regulation (Antonson & Xanthopoulos 1995, Hanlon et al 2000, Jacob & Stanley 2001, Bamberger et al 2004, Lin et al 2005, Chakrabarty & Roberts 2007, Hung et al 2010. We have shown that a site in the CS-A enhancer region can bind at least one member (Elk-1) of the Ets family.…”

“…Furthermore, our array analysis of chromosome 17 sequences in human placental chromatin provides evidence for the existence of a differential C/EBP equilibrium on the AF-1A versus AF-1B regions. C/EBPb is the primary C/EBP species in the placenta and specifically the villous syncytiotrophoblasts versus cytotrophoblasts (Bamberger et al 2004), and was, thus, targeted for assessment. C/EBPb 'intervals', indicating transcription factor binding in situ, were detected in both the CS-A and CS-B genes.…”

“…C/EBPb was targeted for examination based on its high level of placental expression, particularly during late pregnancy (Bamberger et al 2004). C/EBPb 'intervals', indicating transcription factor binding in situ, were detected in both the CS-A and CS-B genes (Fig.…”

Selective Activation of Trophoblast-specific PLAC1 in Breast Cancer by CCAAT/Enhancer-binding Protein β (C/EBPβ) Isoform 2

“…PLAC1 Is Selectively Activated by C/EBP␤ Isoform 2-Constitutive expression of C/EBP␤ has been reported in several human tissues, including liver, lung, ovary, placenta, and breast epithelial cells (27)(28)(29)(30). These data required reanalysis as they did not comply with the highly specific expression of C/EBP␤-regulated PLAC1 in the trophoblastic lineage of placental tissue.…”

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

“…Furthermore, C/EBP␤ was shown to associate with the CS 3Ј-enhancer regions in human term placenta chromatin in situ, suggesting a possible role in vivo (33). C/EBP␤ levels increase in human term placenta and like CS and GH-V are also linked to villous syncytiotrophoblast versus cytotrophoblasts (37). A physiological role for C/EBP␤ in placenta morphogenesis is suggested based on genetic deletion of C/EBP family members in mice (38 -40).…”