MBD5 and MBD6 couple DNA methylation to gene silencing through the J-domain protein SILENZIO
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 methyl-CpG binding domain proteins, MBD5 and MBD6, that are recruited to chromatin by recognition of CG methylati...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2021-06, Vol.372 (6549), p.1434-1439 |
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| creator | Ichino, Lucia Boone, Brandon A Strauskulage, Luke Harris, C Jake Kaur, Gundeep Gladstone, Matthew A Tan, Maverick Feng, Suhua Jami-Alahmadi, Yasaman Duttke, Sascha H Wohlschlegel, James A Cheng, Xiaodong Redding, Sy Jacobsen, Steven E |
| description | 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
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. |
| doi_str_mv | 10.1126/science.abg6130 |
| format | Article |
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| subjects | Deoxyribonucleic acid DNA DNA methylation Gene silencing Genes Proteins |
| title | MBD5 and MBD6 couple DNA methylation to gene silencing through the J-domain protein SILENZIO |
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