DNA demethylases constrain multigenerational methylome and transcriptome divergence
- 1University of California, Berkeley
Abstract
In plants, animals and fungi, DNA methylation is important for the silencing of repetitive DNA and impacts the expression of a subset of genes. DNA methylation landscapes exhibit a high degree of stability over generations, yet this stability is the product of multiple dynamic methylation and demethylation pathways. How these dynamic pathways function over longer multigenerational timescales is unclear. To address this, we inbred quadruple DNA demethylase Arabidopsis mutants and closely related wild type lines for nine generations by single-seed descent. In inbred mutant lines, methylation gains accumulated across generations, with regions of preexisting methylation becoming progressively reinforced or spreading to proximal sequences. Additionally, each inbred line possessed hundreds of de novo methylation gains in unmethylated regions. Two-thirds of all methylation gains and 85% of de novo methylated loci were unique to only one inbred line, suggesting a high degree of stochasticity in multigenerational methylation dynamics. Individual inbred lines also exhibited substantial divergence in both their transcriptomes and small RNA profiles. Our data lead to a model in which DNA demethylases constrain the epigenome and transcriptome space accessible over multigenerational timescales. Long-term loss of DNA demethylase activity causes lineages to drift further apart to more diverged epigenetic landscapes.
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BibTeX
@misc{dmitrieva2026demethylases,
title = {{DNA demethylases constrain multigenerational methylome and transcriptome divergence}},
author = {A. D. Dmitrieva and K. I. Christensen and B. P. Williams},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.762914},
url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762914v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - DNA demethylases constrain multigenerational methylome and transcriptome divergence
AU - A. D. Dmitrieva
AU - K. I. Christensen
AU - B. P. Williams
PY - 2026
DA - 2026/10/29
PB - bioRxiv
DO - 10.64898/2026.10.29.762914
UR - https://www.biorxiv.org/content/10.64898/2026.10.29.762914v1
AB - In plants, animals and fungi, DNA methylation is important for the silencing of repetitive DNA and impacts the expression of a subset of genes. DNA methylation landscapes exhibit a high degree of stability over generations, yet this stability is the product of multiple dynamic methylation and demethylation pathways. How these dynamic pathways function over longer multigenerational timescales is unclear. To address this, we inbred quadruple DNA demethylase Arabidopsis mutants and closely related wild type lines for nine generations by single-seed descent. In inbred mutant lines, methylation gains accumulated across generations, with regions of preexisting methylation becoming progressively reinforced or spreading to proximal sequences. Additionally, each inbred line possessed hundreds of de novo methylation gains in unmethylated regions. Two-thirds of all methylation gains and 85% of de novo methylated loci were unique to only one inbred line, suggesting a high degree of stochasticity in multigenerational methylation dynamics. Individual inbred lines also exhibited substantial divergence in both their transcriptomes and small RNA profiles. Our data lead to a model in which DNA demethylases constrain the epigenome and transcriptome space accessible over multigenerational timescales. Long-term loss of DNA demethylase activity causes lineages to drift further apart to more diverged epigenetic landscapes.
ER -