Structure and Regulation of Eukaryotic 5mC and 6mA DNA Methyltransferases

Дата публикации: 04-08-2026 00:00:00

DNA methylation is a fundamental epigenetic mechanism that shapes genome function, chromatin organization, and cellular differentiation. Although the regulation of 5-methylcytosine (5mC) in higher eukaryotes has been extensively studied, key questions remain regarding how distinct DNA methyltransferases recognize DNA substrates under different chromatin contexts. This dissertation investigates the structure and regulation of representative eukaryotic DNA methyltransferases that establish either 5mC or N6-methyladenine (6mA). First, biochemical analysis of the Neurospora crassa cytosine methyltransferase Defective-In-Methylation-2 (DIM2) shows that its activation is tightly controlled by heterochromatin factors. The highly activated DIM2 requires the cooperativity between HP1 and H3K9me3. Three cryo-EM structures reveal how these multivalent inputs enable region-specific DNA methylation. Second, structural characterization of the Tetrahymena thermophila N6-adenine methyltransferase...

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