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> Controls over methylation expression is complex:
> 
> https://science.sciencemag.org/content/372/6549/1434
> 
> Abstract:
> "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."
> 
> From the discussion: 
> 
> "In conclusion, this work identifies a pathway that links DNA methylation to silencing of sites marked by CG methylation. The characterization of the methyl-binding proteins MBD5 and MBD6 shows that they likely act through a mechanism distinct from that of known MBD proteins in animals. The identification of the J-domain protein SILENZIO as a silencing effector further suggests that gene repression downstream of methylation is linked to chaperone activity, and this new pathway is likely to be conserved among divergent plant lineages.
> 
> Comment:  so complex, it had to be designed. The molecular chaperones act like feedback loops.