MBD2 couples DNA methylation to transposable element silencing during male gametogenesis

Shuya Wang; Ming Wang; Lucia Ichino; Brandon A Boone; Zhenhui Zhong; Ranjith K Papareddy; Evan K Lin; Jaewon Yun; Suhua Feng; Steven E Jacobsen

doi:10.1038/s41477-023-01599-3

MBD2 couples DNA methylation to transposable element silencing during male gametogenesis

Nat Plants. 2024 Jan;10(1):13-24. doi: 10.1038/s41477-023-01599-3. Epub 2024 Jan 15.

Authors

Shuya Wang^{1

2}, Ming Wang^{1

2

3}, Lucia Ichino^{1

2

4}, Brandon A Boone^{1

2}, Zhenhui Zhong^{1

2}, Ranjith K Papareddy², Evan K Lin², Jaewon Yun², Suhua Feng^{1

2

5}, Steven E Jacobsen^{6

7

8

9}

Affiliations

¹ Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA.
² Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
³ State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
⁴ Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.
⁵ Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA. jacobsen@ucla.edu.
⁷ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA. jacobsen@ucla.edu.
⁸ Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA. jacobsen@ucla.edu.
⁹ Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA, USA. jacobsen@ucla.edu.

Abstract

DNA methylation is an essential component of transposable element (TE) silencing, yet the mechanism by which methylation causes transcriptional repression remains poorly understood^1-5. Here we study the Arabidopsis thaliana Methyl-CpG Binding Domain (MBD) proteins MBD1, MBD2 and MBD4 and show that MBD2 acts as a TE repressor during male gametogenesis. MBD2 bound chromatin regions containing high levels of CG methylation, and MBD2 was capable of silencing the FWA gene when tethered to its promoter. MBD2 loss caused activation at a small subset of TEs in the vegetative cell of mature pollen without affecting DNA methylation levels, demonstrating that MBD2-mediated silencing acts strictly downstream of DNA methylation. TE activation in mbd2 became more significant in the mbd5 mbd6 and adcp1 mutant backgrounds, suggesting that MBD2 acts redundantly with other silencing pathways to repress TEs. Overall, our study identifies MBD2 as a methyl reader that acts downstream of DNA methylation to silence TEs during male gametogenesis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

CpG Islands
DNA Methylation*
DNA Transposable Elements* / genetics
Gametogenesis / genetics
Promoter Regions, Genetic

Substances

DNA Transposable Elements

Grants and funding

R35 GM130272/GM/NIGMS NIH HHS/United States