The Role and Regulatory Mechanism of ZSCAN4 in Early Embryonic and Pluripotent Stem Cells / 中国生物化学与分子生物学报

ABSTRACT

Zinc finger and SCAN domain containing 4 (ZSCAN4) is specifically expressed as a DNA-binding protein in 2-cell stage embryos and embryonic stem cells. ZSCAN4 regulates early embryonic development by promoting DNA damage repair and correcting chromosomal abnormalities during zygotic genome activation (ZGA) to maintain genomic and chromosomal integrity in preimplantation embryos. During the transition of mouse embryonic stem cells (mESCs) to 2-cell-like cells, ZSCAN4 interacts with ATP-dependent chromatin remodelers to regulate the activity of murine endogenous retroviral L enhancers, and activate the expression of peripheral 2-cell-phase genes to promote the transition of embryonic stem cells to 2-cell-like cells. ZSCAN4 can also promote telomere reorganization and telomere extension by reducing DNA methylation levels to mediate heterochromatin silencing, maintain genome stability and the infinite self-renewal capacity and pluripotency of pluripotent stem cells, and promote mESCs transition to embryonic 2-cell-like cells. In addition, ZSCAN4 can also reactivate early embryonic genes in reprogramming, and significantly increase the generation efficiency of induced pluripotent stem cells (iPSCs). ZSCAN4 reduces DNA damage during iPSCs formation, and preserves genome stability by lengthening telomeres, thereby promoting the generation of high-quality iPSCs without genetic defects. This article focuses on the research advances of the biological functions of ZSCAN4 in regulating early embryonic development, mediating telomere elongation in pluripotent stem cells, and its role in somatic cell reprogramming, which may provide a reference for optimizing the technology to increase the early embryonic development and maintenance of pluripotent stem cells and iPSC generation.