Zinc finger and SCAN domain containing 4 (ZSCAN4) (ZSCAN4)

Zinc finger and SCAN domain containing 4 (ZSCAN4) is a transcription factor that plays a critical role in maintaining telomere length and genomic stability in pluripotent stem cells and early embryos (UniProt: Q8NAM6). In CD34+ hematopoietic stem cells (HSCs), ZSCAN4 is transiently expressed to facilitate telomere elongation through a recombination-based mechanism, which is distinct from the telomerase-dependent pathway (PubMed: 20336070). This function is vital for preserving the self-renewal capacity of HSCs and preventing cellular senescence, particularly under conditions of replicative stress or aging (PubMed: 27105314). While there are currently no FDA-approved drugs targeting ZSCAN4, it is being actively investigated as a therapeutic target for bone marrow failure syndromes and for the rejuvenation of stem cells prior to transplantation using transient mRNA delivery (PubMed: 31589155). The ability of ZSCAN4 to repair DNA damage and reset telomere length makes it a high-interest target in regenerative medicine, although its potential to promote survival in cancer cells necessitates careful therapeutic window management (PubMed: 24906167).

Other names

ZNF494Zinc finger protein 494ZSCAN4 gene

Transient expression of ZSCAN4 induces telomere lengthening through a recombination-based mechanism (ALT-like) and promotes genomic stability by recruiting DNA repair machinery.