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

doi:10.1126/science.abg6130

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

Research output: Contribution to journal › Article › peer-review

65 Scopus citations

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.

Original language	English
Pages (from-to)	1434-1439
Number of pages	6
Journal	Science
Volume	372
Issue number	6549
DOIs	https://doi.org/10.1126/science.abg6130
State	Published - Jun 25 2021
Externally published	Yes

Funding

This work was supported by NIH R35 GM130272 to S.E.J., the UCSF Program for Breakthrough Biomedical Research and the Sandler Foundation to S.R., NIH R01 GM089778 to J.A.W., NIH R35 GM134744 and CPRIT RR160029 to X.C. (who is a CPRIT Scholar in Cancer Research), NIH/NIGMS K99 GM135515 to S.H.D, the Philip Whitcome Pre-Doctoral Fellowship in Molecular Biology to L.I., and the Ruth L. Kirschstein National Research Service Award GM007185 to B.A.B.. S.E.J. is an investigator of the Howard Hughes Medical Institute.

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Ichino, L., Boone, B. A., Strauskulage, L., Harris, C. J., Kaur, G., Gladstone, M. A., Tan, M., Feng, S., Jami-Alahmadi, Y., Duttke, S. H., Wohlschlegel, J. A., Cheng, X., Redding, S., & Jacobsen, S. E. (2021). MBD5 and MBD6 couple DNA methylation to gene silencing through the J-domain protein SILENZIO. Science, 372(6549), 1434-1439. https://doi.org/10.1126/science.abg6130

@article{970bc43574cb4b1e825235eeb1eda3d5,

title = "MBD5 and MBD6 couple DNA methylation to gene silencing through the J-domain protein SILENZIO",

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.",

author = "Lucia Ichino and Boone, \{Brandon A.\} and Luke Strauskulage and Harris, \{C. Jake\} and Gundeep Kaur and Gladstone, \{Matthew A.\} and Maverick Tan and Suhua Feng and Yasaman Jami-Alahmadi and Duttke, \{Sascha H.\} and Wohlschlegel, \{James A.\} and Xiaodong Cheng and Sy Redding and Jacobsen, \{Steven E.\}",

note = "Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved.",

year = "2021",

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doi = "10.1126/science.abg6130",

language = "English",

volume = "372",

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T1 - MBD5 and MBD6 couple DNA methylation to gene silencing through the J-domain protein SILENZIO

AU - Ichino, Lucia

AU - Boone, Brandon A.

AU - Strauskulage, Luke

AU - Harris, C. Jake

AU - Kaur, Gundeep

AU - Gladstone, Matthew A.

AU - Tan, Maverick

AU - Feng, Suhua

AU - Jami-Alahmadi, Yasaman

AU - Duttke, Sascha H.

AU - Wohlschlegel, James A.

AU - Cheng, Xiaodong

AU - Redding, Sy

AU - Jacobsen, Steven E.

PY - 2021/6/25

Y1 - 2021/6/25

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85108725443

U2 - 10.1126/science.abg6130

DO - 10.1126/science.abg6130

M3 - Article

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AN - SCOPUS:85108725443

SN - 0036-8075

VL - 372

SP - 1434

EP - 1439

JO - Science

JF - Science

IS - 6549

ER -

MBD5 and MBD6 couple DNA methylation to gene silencing through the J-domain protein SILENZIO

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