DNA Methylation Triggers Tighter Wrap In Nucleosomes

A close look at how the structure of nucleosomes changes upon DNA methylation will help scientists unravel how genomic methylation represses and even silences gene expression. Eukaryotes rely on nucleosomes—consisting of genomic DNA wound around protein spools—to pack genomic DNA into a small space. Methylation of genomic DNA at specific cytosine bases can hinder and even stop transcription. Various proposals have been floated for how methyl marks might trigger these effects. For example, there’s evidence they somehow compress DNA packing such that the transcription machinery can’t easily gain access to the genome. To get a better idea of how methylation might change the structure of nucleosomes, Tae-Hee Lee and Ju Yeon Lee of Pennsylvania State University used fluorescence resonance energy transfer, or FRET, to probe the structure of individual nucleosomes. When methylated, the DNA wraps tighter around its protein spool (J. Am. Chem. Soc., DOI: 10.1021/ja210273w). They suggest this tighter wrapping, along with the resulting topological change in the wrapped DNA, may directly contribute to methylation-induced genomic repression and silencing.