SET domain-mediated lysine methylation in lower organisms regulates growth and transcription in hosts

Su(var)3‐9, Enhancer‐of‐zeste, Trithorax (SET) domain–mediated lysine methylation, one of the major epigenetic marks, has been found to regulate chromatin‐mediated gene transcription. Published studies have established further that methylation is not restricted to nuclear proteins but is involved in many cellular processes, including growth, differentiation, immune regulation, and cancer progression. The biological complexity of lysine methylation emerges from its capacity to cause gene activation or gene repression owing to the specific position of methylated‐lysine moieties on the chromatin. Accumulating evidence suggests that despite the absence of chromatin, viruses and prokaryotes also express SET proteins, although their functional roles remain relatively less investigated. One possibility could be that SET proteins in lower organisms have more than one biological function, for example, in regulating growth or in manipulating host transcription machinery in order to establish infection. Thus, elucidating the role of an SET protein in host–pathogen interactions requires a thorough understanding of their functions. This review discusses the biological role of lysine methylation in prokaryotes and lower eukaryotes, as well as the underlying structural complexity and functional diversity of SET proteins.