Abstract
The transcription factor ZBED1 is highly expressed in trophoblast cells, but its functions in the processes of trophoblast and placental biology remain elusive. Here, we characterized the role of ZBED1 in trophoblast cell differentiation using an in vitro BeWo cell model. We demonstrate that ZBED1 is enhanced in its expression early after forskolin-induced differentiation of BeWo cells and regulates many of the genes that are differentially expressed as an effect of forskolin treatment. Specifically, genes encoding markers for the differentiation of cytotrophoblast into syncytiotrophoblast and factors essential for trophoblast cell fusion and invasion were negatively regulated by ZBED1, indicating that ZBED1 might be important for maintaining a steady pool of cytotrophoblast cells. In addition, ZBED1 affected genes involved in the regulation of trophoblast cell survival and apoptosis, in agreement with the observed increase in apoptosis upon knockdown of ZBED1 in forskolin-treated BeWo cells. In addition, genes implicated in the differentiation, recruitment, and function of innate immune cells by the placenta were affected by ZBED1, further suggesting a role for this protein in the regulation of maternal immune tolerance. In conclusion, our study implicates ZBED1 in major biological processes of placental biology.
Highlights
The human zinc finger BED domain-containing protein 1 (ZBED1), known as the human DNA replication-related element-binding factor, is a transcription factor suggested to regulate cell cycle progression and proliferation [1,2]
ZBED1 expression is induced in the G1-S phase and regulates the expression of genes such as histone 1 (H1) and ribosomal proteins [1,4], which might be facilitated by regulating the nucleosome remodeling and deacetylase complex (NuRD) [5]
ZBED1 Expression Is Upregulated during Trophoblast Cell Differentiation
Summary
The human zinc finger BED domain-containing protein 1 (ZBED1), known as the human DNA replication-related element-binding factor (hDREF), is a transcription factor suggested to regulate cell cycle progression and proliferation [1,2]. Initial database searches have mapped the binding sequence of ZBED1 to various promoters of genes involved in DNA replication and repair, cell cycle regulation, and transcription [1], suggesting that ZBED1 is required to maintain the basal transcription machinery and is important for normal cell growth and proliferation. A recent study has elucidated a link between ZBED1 overexpression in gastric cancer and poor prognosis and further demonstrated that ectopic expression of ZBED1 promotes cell proliferation and colony formation abilities of gastric cancer cell lines [6]. Investigation of ZBED1 in developmental contexts of the human organism, such as the placenta, might elucidate additional functions of ZBED1
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