Methylations are epigenetic modification that, in eukaryotes, regulates processes as cell differentiation, and embryogenesis, while in prokaryotes can have a role in self recognition, protecting the DNA from being cleaved by the restriction endonuclease system, or for gene regulation. The first function is controlled by the restriction methylation system while the second by Orphan MTases as Dam and CcrM.
CcrM role have been characterized in the marine model organism Caulobacter crescentus, which is suitable for the study of cell cycle and epigenetics as it asymmetrically divides generating different progeny, a stalked and a swarmer cell, with different phenotypes and gene regulation. The swarmer cell has a single flagellum and polar pili and is characterized by its mobility, while the stacked cell has a stalk and is fixed to the substrate. The stacked cell enters immediately in S-phase, while the swarmer cell stays in G1-phase and will differentiate to a stacked cell before entering the S-phase again.
The stacked cell in S phase will replicate its DNA in a semiconservative manner producing two hemimethylated DNA double strands that will be rapidly methylated by the Methyltransferase CcrM, which is only produced at the end of the S phase. The enzyme will methylate more than 4 thousand 5-GANTC-3 sites in around 20 minutes, and then it will be degraded by the LON protease. This fast methylation plays an important role in the transcriptional control of several genes and controls the cell differentiation. CcrM expression is regulated by the CtrA master regulator, and in addition various 5-GANTC-3 sites methylation sites regulate CcrM expression, which will only occur at the end of the S phase when this sites are hemimethylated. In this process CtrA regulates the expression of CcrM and more than 1000 genes in the pre-divisional state, and SciP prevents the activation of CcrM transcription in non replicative cells.