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H4K20me1 plays a dual role in transcriptional regulation during regeneration and axis patterning of Hydra

The evolution of the first body axis in the animal kingdom and an extensive ability to regenerate makes Hydra, a Cnidarian, an excellent model system for understanding the underlying epigenetic mechanisms. We identify that SETD8 is critical for regeneration due to its interaction with β-catenin to fine-tune the underlying gene regulatory network. Its target histone mark, H4K20me1, colocalizes with transcriptional activation machinery locally at the β-catenin bound TCF/LEF binding sites on the promoters of head-associated genes, marking an epigenetic activation node. Contrastingly, genome-wide analysis of the H4K20me1 occupancy revealed a negative correlation with transcriptional activation. We propose H4K20me1 as a general repressive histone mark in Cnidaria and describe its dichotomous role in transcriptional regulation in Hydra.