MBD5 and MBD6 couple DNA methylation to gene silencing through the J-domain protein SILENZIO
Lucia Ichino, Brandon A. Boone, Luke Strauskulage, C. Jake Harris, Gundeep Kaur, Matthew A. Gladstone, Maverick Tan, Suhua Feng, Yasaman Jami‐Alahmadi, Sascha H. Duttke, James A. Wohlschlegel, Xiaodong Cheng, Sy Redding, Steven E. Jacobsen
Abstract
methyl-CpG binding domain proteins, MBD5 and MBD6, that are recruited to chromatin by recognition of CG methylation, and redundantly repress a subset of genes and transposons without affecting DNA methylation levels. These methyl-readers recruit a J-domain protein, SILENZIO, that acts as a transcriptional repressor in loss-of-function and gain-of-function experiments. J-domain proteins often serve as co-chaperones with HSP70s. Indeed, we found that SILENZIO's conserved J-domain motif was required for its interaction with HSP70s and for its silencing function. These results uncover an unprecedented role of a molecular chaperone J-domain protein in gene silencing downstream of DNA methylation.