Methylating the DNA of the most repressed: special access required

Abstract

A new study (Zemach et al., 2013) suggests that the chromatin remodeling ATPase DDM1 is specifically required for cytosine methylation at linker histone H1-associated heterochromatin, facilitating access by three cytosine methyltransferases, including a previously uncharacterized CHH methylase, CMT2.

A model for nucleosome sliding facilitated by DNA translocase activity of DDM1. Linker Histone H1 (yellow) is thought to decrease nucleosome mobility by interacting with DNA at the entry and exit points of each nucleosome core particle (blue) and promoting tight packing of nucleosomes. Genetic evidence of Zemach et al. suggests that DDM1 is needed to counteract the effects of H1 for cytosine methylation. The model depicts one possibility to explain the genetic results, consistent with other chromatin remodeling ATPases, whereby DDM1overcomes the DNA binding energy of H1 to loop out DNA from the surface of nucleosome. Translocation of the looped out DNA around the nucleosome transiently generates a longer linker on the other side of the nucleosome, where DNA methyltransferases (MTAse) might gain access and methylate the DNA (orange hexagons). Concerted action of multiple DDM1 translocases could effectively slide DNA through the nucleosomes like rope through a series of pulleys.