There’s many ways to keep it classy, and while the recent Royal Wedding has demonstrated that some families illustrate their style with an eclectic taste for hats and fascinators, the CLASSY family of chromatin remodeling factors has just out-classed them with its chromatin tastes that shape RNA-directed DNA methylation.
In Arabidopsis thaliana, RNA Pol-IV triggers the biogenesis of 24-nt siRNAs that direct DNA methylation in a loci-specific manner. Now, new research from the lab of Julie Law at the Salk Institute (California, USA) adds some class to the story by uncovering a fundamental role for four putative chromatin remodeling factors (CLASSY 1-4).
Here’s what they discovered:
- Small RNA profiling of CLASSY mutants uncovered their roles as loci-specific regulators of 24-nt siRNAs, which act both individually and synergistically
- First author Ming Zhou adds, “In the CLASSY quadruple mutants, the Pol-IV signal completely disappears—essentially no siRNAs are made. This is very strong evidence that CLASSYs are required for Pol-IV function”
- Whole-genome bisulfite sequencing of the mutants revealed that the CLASSYs regulate both global and locus-specific DNA methylation
- CHH methylation represents the most affected type of DNA methylation
- ChIP-seq of a tagged Pol-IV line crossed with the CLASSY mutants demonstrated that the CLASSY family is required for the interaction of Pol-IV with chromatin
- Finally, crosses with mutants for specific DNA methylation contexts and repressive histone modifications showed that the proteins associate with different chromatin modifications from another, such as CG methylation (CLASSY1 & CLASSY2) and H3K9me (CLASSY1 & CLASSY2)
Overall, the CLASSY family acts individually and synergistically to regulate the biogenesis of 24-nt siRNAs from Pol-IV, which function in the RNA-directed DNA methylation pathway that regulates loci-specific DNA methylation patterns.
Senior author Julie Law shares, “If we want to understand how differences in DNA methylation patterns can cause developmental defects in plants, or diseases like cancer in humans, we need to understand how DNA methylation is targeted to specific regions of the genome under normal conditions. Until now, factors able to control methylation in such a precise manner have been elusive. The CLASSYs are a part of a large superfamily that is common to both plants and animals. We hope that by understanding how specific methylation patterns are generated in plants, we can provide insights into how DNA methylation is regulated in other organisms.”
Learn all about how to keep it CLASSY over at Nature Genetics, May 2018.