Several aspects of the proposal, which aims to expand open access, require serious discussion and, in some cases, a rethink.
Image credit: Dave Cutler (artist).
New Research In
Physical Sciences
Featured Portals
Articles by Topic
Biological Sciences
Featured Portals
Articles by Topic
Contributed by Steven E. Jacobsen, August 2, 2018 (sent for review June 11, 2018; reviewed by Roger B. Deal and Zhanxin Wang)
Significance
Plant SUVH family H3K9 methyltransferases play a key role in connecting the two epigenetic silencing marks, DNA methylation and H3K9me2. However, the regulation of SUVH protein activities and their precise role in the regulation of DNA methylation remains unclear. In this research, we performed a comprehensive investigation into the structure, biochemistry, and in vivo targeting characteristics of SUVH histone methyltransferases. For binding methylated DNA, we reveal that the SUVH family proteins possess a unique thumb loop-dependent base-flipping mechanism. For methyltransferase function, we reveal that SUVH6 is regulated by a dynamic autoinhibitory domain. Finally, our in vitro DNA-binding assays combined with ChIP-seq data uncover mechanisms to help explain context-biased non-CG DNA methylation in plants.
Abstract
DNA methylation functions in gene silencing and the maintenance of genome integrity. In plants, non-CG DNA methylation is linked through a self-reinforcing loop with histone 3 lysine 9 dimethylation (H3K9me2). The plant-specific SUPPRESSOR OF VARIEGATION 3–9 HOMOLOG (SUVH) family H3K9 methyltransferases (MTases) bind to DNA methylation marks and catalyze H3K9 methylation. Here, we analyzed the structure and function of Arabidopsis thaliana SUVH6 to understand how this class of enzyme maintains methylation patterns in the genome. We reveal that SUVH6 has a distinct 5-methyl-dC (5mC) base-flipping mechanism involving a thumb loop element. Autoinhibition of H3 substrate entry is regulated by a SET domain loop, and a conformational transition in the post-SET domain upon cofactor binding may control catalysis. In vitro DNA binding and in vivo ChIP-seq data reveal that the different SUVH family H3K9 MTases have distinct DNA binding preferences, targeting H3K9 methylation to sites with different methylated DNA sequences, explaining the context biased non-CG DNA methylation in plants.
Footnotes
↵1X.L. and C.J.H. contributed equally to this work.
- ↵2To whom correspondence may be addressed. Email: jacobsen{at}ucla.edu or jmdu{at}sibs.ac.cn.
Author contributions: Z.W., S.E.J., and J.D. designed research; X.L., C.J.H., W.C., R.L., B.J., and S.L. performed research; Z.Z., S.E.J., and J.D. analyzed data; and S.E.J. and J.D. wrote the paper.
Reviewers: R.B.D., Emory University; and Z.W., Beijing Normal University.
Conflict of interest statement: S.E.J. and Roger B. Deal were coauthors on a 2016 paper. They did not have any direct research collaboration on this work.
Data deposition: X-ray structures have been deposited in the RCSB Protein Data Bank with the accession codes: 6A5K, 6A5M, and 6A5N. The high throughput sequencing data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE114009).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1809841115/-/DCSupplemental.
Published under the PNAS license.
Log in using your username and password
Purchase access
You may purchase access to this article. This will require you to create an account if you don't already have one.
Mechanistic insights into plant SUVH family H3K9 methyltransferases and their binding to context-biased non-CG DNA methylation
Sign up for Article Alerts
Jump to section
You May Also be Interested in
Several large or long-lived animals seem strangely resistant to developing cancer. Elucidating the reasons why could lead to promising cancer-fighting strategies in humans.
Image credit: Shutterstock.com/ronnybas frimages.
PNAS Profile of NAS member and biochemist Hao Wu
A study suggests a putative gene-expression hallmark common to monogamous male vertebrates of some species, namely cichlid fishes, dendrobatid frogs, passeroid songbirds, common voles, and deer mice, and identifies 24 candidate genes potentially associated with monogamy.
Image courtesy of Yusan Yang (University of Pittsburgh, Pittsburgh).
Physical and social well-being in old age are linked to self-assessments of life worth, and a spectrum of behavioral, economic, health, and social variables may influence whether aging individuals believe they are leading meaningful lives.
Image courtesy of Pixabay/MabelAmber.