DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes

Living cells add chemical tags to their DNA to regulate which genes are switched on or off at any given time. These tags include methyl groups added to one of the letters of the DNA code called cytosine. Both plants and mammals need cytosine methylation to develop properly. This methylation also keeps sections of foreign DNA that may have invaded the cell in check. DNA inside the cell is tightly packed, wrapped around proteins to form spool-like structures called nucleosomes. Between each nucleosome is a short DNA segment called a linker region. The DNA wound into nucleosomes is generally inaccessible to other proteins, such as those that add methyl groups. Yet, in flowering plants and mammals, cytosine methylation occurs in both nucleosomes and in linker regions. It was not clear how DNA could be modified in the restrained setting of nucleosomes. Enzymes called nucleosome remodelers can loosen nucleosomes to allow other proteins to reach the DNA. Lyons and Zilberman asked whether cytosine methylation occurs on the nucleosome-bound DNA or if it requires enzymes like these to free the DNA from the constraints of the nucleosome. The experiments involved a plant called Arabidopsis thaliana and mouse cells grown in the laboratory. In mutant plants lacking a nucleosome remodeler called DDM1, cytosine methylation occurred in the linker regions but not in the nucleosomes. Mouse cells lacking the mouse version of DDM1 also showed less cytosine methylation in the nucleosomes. These results suggest that nucleosomes are barriers to the enzymes that modify DNA. Nucleosome remodeling enzymes like DDM1 can overcome these obstacles to enable cytosine methylation of nucleosome-wrapped DNA. These findings imply that cytosine methylation is more easily established and maintained on nucleosome-free DNA. Abnormal patterns of DNA methylation have been linked to medical conditions – such as neurological disorders and cancers – and to plant defects that hamper agriculture. A better understanding of the process may in the future lead to ways to correct problems with cytosine methylation in these different contexts.