# Gene body methylation buffers noise in gene expression in plants

**Authors:** Jakub Zastąpiło, Robyn A Emmerson, Liudmila A Mikheeva, Marco Catoni, Ulrike Bechtold, Nicolae Radu Zabet

PMC · DOI: 10.1093/nar/gkag127 · Nucleic Acids Research · 2026-02-17

## TL;DR

Gene body methylation helps reduce random fluctuations in gene expression in plants, especially for essential genes.

## Contribution

This study establishes a functional link between gene body methylation and reduced transcriptional noise in plants.

## Key findings

- Loss of CG methylation increases gene expression noise in mutants.
- Non-CG methylation compensates for noise in plants with complete CG methylation loss.
- Noise buffering is most important for housekeeping genes and less so for stress response genes.

## Abstract

Non-genetic variability in gene expression is an inevitable consequence of the stochastic nature of processes driving transcription and translation. While previous studies demonstrated that gene expression noise is negatively correlated with gene body methylation, the function of this correlation remains poorly understood in multicellular systems. Here, we provide a first functional link between gene body methylation and transcription noise in plants. We investigated a mutant with partial loss of CG methylation (met1-1) and 10 epigenetic recombinant inbred lines (epiRILs) generated by a cross between Col-0 and met1-3 plants, and observed an increase in gene expression noise, but this was not the case in met1-3 with complete loss of CG methylation. Loss of CG methylation in met1-3 could be compensated by a low but significant gain of non-CG methylation that buffers the noise in gene expression. Overall, our results show that gene body methylation has a functional role in reducing variability in transcription in a large subset of housekeeping genes, which require precise expression patterns to meet metabolic requirements. Genes lacking this noise-buffering effect are mainly enriched in stress response, where variability in gene expression can be seen as highly beneficial.

Graphical Abstract

## Full-text entities

- **Genes:** IBM1 (Transcription factor jumonji (jmjC) domain-containing protein) [NCBI Gene 819952] {aka increase in bonsai methylation 1}, CHR23 (homeotic protein regulator) [NCBI Gene 832051] {aka AtCHR23, F7K24.60, F7K24_60, chromatin remodeling 23}, MET1 (methyltransferase 1) [NCBI Gene 834975] {aka DDM2, DECREASED DNA METHYLATION 2, DMT01, DMT1, DNA METHYLTRANSFERASE, DNA METHYLTRANSFERASE 01}, AT4G09784 (histone deacetylase) [NCBI Gene 6240301]
- **Diseases:** CHH (MESH:C535916)
- **Chemicals:** cytosine (MESH:D003596), CV2 (-), phosphate (MESH:D010710), nitrogen (MESH:D009584), agar (MESH:D000362)
- **Species:** Arabidopsis thaliana (mouse-ear cress, species) [taxon 3702], Homo sapiens (human, species) [taxon 9606], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932]
- **Mutations:** 10G -cytosine
- **Cell lines:** Col-0 — Homo sapiens (Human), Childhood T lymphoblastic lymphoma, Cancer cell line (CVCL_4966)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12910109/full.md

## References

80 references — full list in the complete paper: https://tomesphere.com/paper/PMC12910109/full.md

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Source: https://tomesphere.com/paper/PMC12910109