Polycomb Repressive Complex (PRC) group proteins regulate various developmental processes in plants by repressing the target genes via H3K27 trimethylation, whereas their function is antagonized by Trithorax group proteins-mediated H3K4 trimethylation. Tuberization in potato is widely studied, but the role of histone modifications in this process is unknown. Recently, we showed that overexpression of StMSI1 (a PRC2 member) alters the expression of tuberization genes in potato. As MSI1 lacks histone-modification activity, we hypothesized that this altered expression could be caused by another PRC2 member, StE(z)2 (a potential H3K27 methyltransferase in potato). Here, we demonstrate that short-day photoperiod influences StE(z)2 expression in leaf and stolon. Moreover, StE(z)2 overexpression alters plant architecture and reduces tuber yield, whereas its knockdown enhanced the yield. ChIP-sequencing using short-day induced stolons revealed that several tuberization and phytohormone-related genes, such as StBEL5/11/29, StSWEET11B, StGA2OX1 and StPIN1 carry H3K4me3 or H3K27me3 marks and/or are StE(z)2 targets. Interestingly, we noticed that another important tuberization gene, StSP6A is targeted by StE(z)2 in leaves and had increased deposition of H3K27me3 under non-induced (long-day) conditions compared to SD. Overall, we show that StE(z)2 and deposition of H3K27me3 and/or H3K4me3 marks could regulate the expression of key tuberization genes in potato.