Repression of CHROMOMETHYLASE 3 prevents epigenetic collateral damage in Arabidopsis
Abstract
DNA methylation has evolved to silence mutagenic transposable elements (TEs) while typically avoiding the targeting of endogenous genes. Mechanisms that prevent DNA methyltransferases from ectopically methylating genes are expected to be of prime importance during periods of dynamic cell cycle activities including plant embryogenesis. However, virtually nothing is known regarding how DNA methyltransferase activities are precisely regulated during embryogenesis to prevent the induction of potentially deleterious and mitotically stable genic epimutations. Here, we report that microRNA-mediated repression of CHROMOMETHYLASE 3 (CMT3) and the chromatin features that CMT3 prefers help prevent ectopic methylation of thousands of genes during embryogenesis that can persist for weeks afterwards. Our results are also consistent with CMT3-induced ectopic methylation of promoters or bodies of genes undergoing transcriptional activation reducing their expression. Therefore, the repression of CMT3 prevents epigenetic collateral damage on endogenous genes. We also provide a model that may help reconcile conflicting viewpoints regarding the functions of gene-body methylation that occurs in nearly all flowering plants.
Data availability
All sequencing data generated in this study are publicly available at the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO, https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE171198.
-
Repression of CHROMOMETHYLASE 3 Prevents Epigenetic Collateral Damage in ArabidopsisNCBI Gene Expression Omnibus, GSE171198.
-
The embryonic transcriptome of Arabidopsis thalianaNCBI Gene Expression Omnibus, GSE121236.
-
Active DNA demethylation in plant companion cells reinforces transposon methylation in gametesNCBI Gene Expression Omnibus, GSE38935.
-
Natural epigenetic polymorphisms lead to intraspecific variation in Arabidopsis gene imprintingNCBI Gene Expression Omnibus, GSE52814.
-
Genome-wide demethylation of Arabidopsis endospermNCBI Gene Expression Omnibus, GSE15922.
-
DNA methylation dynamics during early plant lifeNCBI Gene Expression Omnibus, GSE85975.
-
Comprehensive analysis of silencing mutants reveals complex regulation of the Arabidopsis methylomeNCBI Gene Expression Omnibus, GSE39901.
-
The Histone Variant H2A.W Defines Heterochromatin and Promotes Chromatin Condensation in ArabidopsisNCBI Gene Expression Omnibus, GSE50942.
-
Non-CG methylation patterns shape the epigenetic landscape in ArabidopsisNCBI Gene Expression Omnibus, GSE51304.
-
Peroxisomal β-oxidation regulates histone acetylation and DNA methylation in ArabidopsisNCBI Gene Expression Omnibus, GSE98214.
-
DNA methylation and histone H1 jointly repress transposable elements and aberrant intragenic transcriptsNCBI Gene Expression Omnibus, GSE122394.
-
MNase analysis of linker histone H1 mutantNCBI Gene Expression Omnibus, GSE113556.
-
DNA methylation-linked chromatin accessibility affects genomic architecture in ArabidopsisNCBI Gene Expression Omnibus, GSE155503.
Article and author information
Author details
Funding
H2020 European Research Council (637888)
- Michael D Nodine
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Papareddy et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,197
- views
-
- 346
- downloads
-
- 16
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Genetics and Genomics
Becker muscular dystrophy (BMD), an X-linked muscular dystrophy, is mostly caused by an in-frame deletion of Duchenne muscular dystrophy (DMD). BMD severity varies from asymptomatic to severe, associated with the genotype of DMD. However, the underlying mechanisms remain unclear. We established BMD mice carrying three representative exon deletions: ex45–48 del., ex45–47 del., and ex45–49 del. (d45–48, d45–47, and d45–49), with high frequencies and different severities in the human BMD hotspot. All three BMD mice showed muscle weakness, muscle degeneration, and fibrosis, but these changes appeared at different times for each exon deletion, consistent with the severities obtained by the natural history study of BMD. BMD mice showed site-specific muscle changes, unlike mdx mice, which showed diffuse muscle changes, and we demonstrated selective type IIa fiber reduction in BMD mice. Furthermore, BMD mice showed sarcolemmal neuronal nitric oxide synthase (nNOS) reduction and morphological capillary changes around type IIa fibers. These results suggest that capillary changes caused by nNOS reduction may be associated with the mechanism of skeletal muscle degeneration and type IIa fiber reduction in BMD mice. BMD mice may be useful in elucidating the pathomechanisms and developing vascular targeted therapies for human BMD.
-
- Genetics and Genomics
- Microbiology and Infectious Disease
Evolution of gene expression frequently drives antibiotic resistance in bacteria. We had previously (Patel and Matange, eLife, 2021) shown that, in Escherichia coli, mutations at the mgrB locus were beneficial under trimethoprim exposure and led to overexpression of dihydrofolate reductase (DHFR), encoded by the folA gene. Here, we show that DHFR levels are further enhanced by spontaneous duplication of a genomic segment encompassing folA and spanning hundreds of kilobases. This duplication was rare in wild-type E. coli. However, its frequency was elevated in a lon-knockout strain, altering the mutational landscape early during trimethoprim adaptation. We then exploit this system to investigate the relationship between trimethoprim pressure and folA copy number. During long-term evolution, folA duplications were frequently reversed. Reversal was slower under antibiotic pressure, first requiring the acquisition of point mutations in DHFR or its promoter. Unexpectedly, despite resistance-conferring point mutations, some populations under high trimethoprim pressure maintained folA duplication to compensate for low abundance DHFR mutants. We find that evolution of gene dosage depends on expression demand, which is generated by antibiotic and exacerbated by proteolysis of drug-resistant mutants of DHFR. We propose a novel role for proteostasis as a determinant of copy number evolution in antibiotic-resistant bacteria.