Telomeres are repetitive sequences at the ends of chromosomes that protect the coding regions of DNA. Telomeres shorten with every cell division and therefore operate as a biological clock. Thus, factors regulating telomeric chromatin impact cell replicative lifespan, tumor formation and growth. The murine Zinc Finger and SCAN Domain Containing 4 (mZscan4) promotes telomere homeostasis and genomic stability in mouse embryonic stem cells (mESCs). A transient expression of mZscan4 was shown to correlate with chromatin de-repression in mESCs. However, the function of human ZSCAN4 in its contribution to the epigenetic landscape changes at telomeric chromatin remains to be determined. In this study, we defined the effect of ZSCAN4 on histone 3 and 4 hyperacetylation at the telomere region which is associated with telomere extension. Understanding the mechanism by which ZSCAN4 affects the telomeric chromatin is important for designing new therapeutic approaches to target cancer cell replicative lifespan.