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

The evolution of the first body axis in the animal kingdom and its extensive ability to regenerate makes Hydra, a Cnidarian, an excellent model system for understanding the underlying epigenetic mechanisms. We identify that monomethyltransferase SETD8 is critical for regeneration in Hydra because of its conserved interaction with ß-catenin to fine-tune the associated gene regulatory network. Inhibition of SETD8 activity abolishes head and foot regeneration in Hydra Furthermore, we show that H4K20me1, the histone mark imparted by SETD8, colocalizes with the transcriptional activation machinery locally at the ß-catenin-bound TCF/LEF-binding sites on the promoters of head-associated genes, marking an epigenetic activation mode. In contrast, genome-wide analysis of the H4K20me1 occupancy revealed a negative correlation with transcriptional activation. We propose that H4K20me1 acts as a general repressive histone mark in Cnidaria and describe its dichotomous role in transcriptional regulation in Hydra.

DNA methylation and regulation of gene expression: Guardian of our health.

One of the most critical epigenetic signatures present in the genome of higher eukaryotes is the methylation of DNA at the C-5 position of the cytosine ring. Based on the sites of DNA methylation in a locus, it can serve as a repressive or activation mark for gene expression. In a crosstalk with histone modifiers, DNA methylation can consequently either inhibit binding of the transcription machinery or generate a landscape conducive for transcription. During developmental phases, the DNA methylation pattern in the genome undergoes alterations as a result of regulated balance between de novo DNA methylation and demethylation. Resultantly, differentiated cells inherit a unique DNA methylation pattern that fine tunes tissue-specific gene expression. Although apparently a stable epigenetic mark, DNA methylation is actually labile and is a complex reflection of interaction between epigenome, genome and environmental factors prior to birth and during progression of life. Recent findings indicate that levels of DNA methylation in an individual is a dynamic outcome, strongly influenced by the dietary environment during germ cell formation, embryogenesis and post birth exposures. Loss of balances in DNA methylation during developmental stages may result in imprinting disorders, while at any later stage may lead to increased predisposition to various diseases and abnormalities. This review aims to provide an outline of how our epigenome is uniquely guided by our lifetime of experiences beginning in the womb and how understanding it better holds future possibilities of improvised clinical applications.