MBD5 and MBD6 Couple DNA Methylation to Gene Silencing Through the J-domain Protein SILENZIO

Methyl readers that repress transcription DNA methylation is a conserved epigenetic mark required for gene silencing in many different organisms. However, how the methyl mark is able to silence genes is still largely unknown. Ichino et al. discovered two Arabidopsis proteins named MBD5 and MBD6 that are recruited to DNA by direct recognition of methylation. These methyl readers recruit the class C J-domain protein SILENZIO to chromatin to silence methylated genes and transposons. SILENZIO likely acts through its interaction with heat shock chaperone proteins. Science, abg6130, this issue p. 1434 Two CG-specific DNA methyl readers redundantly repress methylated genes and transposons by recruiting a molecular chaperone protein in Arabidopsis. DNA methylation is associated with transcriptional repression of eukaryotic genes and transposons, but the downstream mechanism of gene silencing is largely unknown. Here, we describe two Arabidopsis thaliana 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.