Role of Histone Methyltransferases during Regeneration of Hydra

Hydra, a freshwater polyp of the phylum Cnidaria, has an immense ability to regenerate lost body parts by reorganizing the available tissue without involving cellular proliferation by a process known as morphallaxis. Evoking gene regulatory networks at precise time points is essential to achieve this feat. Epigenetic regulators presumably play the key role in fine-tuning these transcriptional changes by modulating the chromatin topography. However, the role of epigenetic modifiers in shaping the regeneration process in Hydra remains an open question. In this study, we attempted to characterize a number of histone methyltransferases from Hydra and investigated their role during regeneration. Preliminary screening performed using specific pharmacological inhibitors indicated a role of SETD8, an enzyme responsible for deposition of H4K20me1, during Hydra regeneration. Our work demonstrates a significant delay in the tentacle bud emergence and impairment of foot regeneration upon treating Hydra with UNC0379, a substrate-competitive inhibitor of SETD8, in the respective regeneration assays. Interestingly, SETD8 gets transiently upregulated in the regenerating tip during the early time points, i.e. 2 to 8 hours post amputation. Furthermore, ectopic activation of canonical Wnt signaling pathway, which has been well characterized for its role in head organizer function, leads to transcriptional upregulation of SETD8. Taken together, the findings from our study have led to the identification of a critical role played by SETD8 in the morphallactic regeneration of Hydra. Further investigation addressing the role of SETD8 in modulating the target gene regulation by H4K20me1 promises to provide novel insights into the epigenetic control of regeneration process.