Biology subjects

Williams, B. P.

Publications and source records attributed to Williams, B. P..

7 recordsLinked to original sources

bioRxiv2026

DNA demethylases constrain multigenerational methylome and transcriptome divergence

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.

plant biology↗

bioRxiv2026

DNA demethylation suppresses a state of enhanced cellular pluripotency and regeneration competence in Arabidopsis.

The plant kingdom exhibits a wide range of phenotypic variation in capacity to regenerate tissues and organs, from whole-plant vegetative propagation via cuttings, to recalcitrance even under optimized tissue culture. Currently, the molecular pathways underpinning this phenotypic variation are poorly understood. Here, we report that Arabidopsis mutants of the DNA demethylase pathway exhibit dramatically enhanced regeneration and the ability to propagate whole plants from cuttings without the use of exogenous hormones. Vegetatively propagated plants possess a shared regeneration signature of de novo DNA methylation gains at the transcription start sites of many genes, including approximately 30 genes involved in cellular pluripotency and tissue regeneration. These methylation changes can be inherited through sexual reproduction and are associated with exacerbated transcriptomic changes. We propose that loss of the DNA demethylase pathway unlocks a path on the epigenetic landscape towards increased pluripotency and regeneration without the application of exogenous hormones.

plant biology↗

bioRxiv2024

Aging drives a program of DNA methylation decay in plant organs

How organisms age is a question with broad implications for human health. In mammals, DNA methylation is a biomarker for biological age, which may predict age more accurately than date of birth. However, limitations in mammalian models make it difficult to identify mechanisms underpinning age-related DNA methylation changes. Here, we show that the short-lived model plant Arabidopsis thaliana exhibits a loss of epigenetic integrity during aging, causing heterochromatin DNA methylation decay and the expression of transposable elements. We show that the rate of epigenetic aging can be manipulated by extending or curtailing lifespan, and that shoot apical meristems are protected from this aging process. We demonstrate that a program of transcriptional repression suppresses DNA methylation maintenance pathways during aging, and that mutants of this mechanism display a complete absence of epigenetic decay. This presents a new paradigm in which a gene regulatory program sets the rate of epigenomic information loss during aging.

plant biology↗

bioRxiv2022

Dynamic DNA methylation turnover in gene bodies is associated with enhanced gene expression plasticity

BackgroundIn several eukaryotes, DNA methylation occurs within the coding regions of many genes, termed gene body methylation (GbM). Whereas the role of DNA methylation on the silencing of transposons and repetitive DNA is well understood, gene body methylation is not associated with transcriptional repression, and its biological importance has remained unclear. ResultsWe report a newly discovered type of GbM in plants, which is under constitutive addition and removal by dynamic methylation modifiers in all cells, including the germline. Methylation at Dynamic GbM genes is removed by the DRDD demethylation pathway and added by an unknown source of de novo methylation, most likely the maintenance methyltransferase MET1. We show that the Dynamic GbM state is present at homologous genes across divergent lineages spanning over 100 million years, indicating evolutionary conservation. We demonstrate that Dynamic GbM is tightly associated with the presence of a promoter or regulatory chromatin state within the gene body, in contrast to other gene body methylated genes. We find Dynamic GbM is associated with enhanced gene expression plasticity across development and diverse physiological conditions, whereas stably methylated GbM genes exhibit reduced plasticity. Dynamic GbM genes exhibit reduced dynamic range in drdd mutants, indicating a causal link between DNA demethylation and enhanced gene expression plasticity. ConclusionsThis study proposes a new model for GbM in regulating gene expression plasticity, including a newly discovered type of GbM in which increased gene expression plasticity is associated with the activity of DNA methylation writers and erasers and the enrichment of a regulatory chromatin state.

genomics↗

bioRxiv2021

Somatic DNA demethylation generates tissue-specific methylation states and impacts flowering time

Cytosine methylation is a reversible epigenetic modification to DNA. In plants, removal of cytosine methylation is accomplished by the four members of the DME family of 5-methylcytosine DNA glycosylases. Demethylation by DME is critical for seed development. Consequently, determining the function of the entire gene family in somatic tissues by mutant analysis has not been possible. Here, we bypassed the reproductive defects of dme mutants to create somatic quadruple homozygous mutants of the entire DME family. dme; ros1; dml2; dml3 (drdd) leaves exhibit hypermethylated genomes compared to both wild-type plants and rdd triple mutants, indicating functional redundancy among all four demethylases. Targets of demethylation include regions co-targeted by RNA-directed DNA methylation and, surprisingly, CG gene body methylation, indicating dynamic methylation at these little-understood sites. Additionally, many tissue-specific methylation differences are absent in drdd, suggesting a role for active demethylation in generating divergent epigenetic states across wild-type tissues. Furthermore, drdd plants display a striking early flowering phenotype, which is associated with 5 hypermethylation and transcriptional down-regulation of FLOWERING LOCUS C. Active DNA demethylation is therefore required for proper methylation patterning across somatic tissues and defines the epigenetic landscape of both intergenic and coding regions.

plant biology↗

bioRxiv2020

Single nucleus analysis of Arabidopsis seeds reveals new cell types and imprinting dynamics

Seeds are the basis of agriculture, yet their full transcriptional complexity has remained unknown. Here, we employ single-nucleus RNA-sequencing to characterize developing Arabidopsis thaliana seeds, with a focus on endosperm. Endosperm, the site of gene imprinting in plants, mediates the relationship between the maternal parent and embryo. We identify new cell types in the chalazal endosperm region, which interfaces with maternal tissue for nutrient unloading. We further demonstrate that the extent of parental bias of maternally expressed imprinted genes varies with cell cycle phase, and that imprinting of paternally expressed imprinted genes is strongest in chalazal endosperm. These data indicate imprinting in endosperm is heterogeneous and suggest that parental conflict, which is proposed to drive the evolution of imprinting, is fiercest at the boundary between filial and maternal tissues.

plant biology↗

bioRxiv2016

Ancient coding sequences underpin the spatial patterning of gene expression in C4 leaves

Photosynthesis is compromised in most plants because an enzymatic side-reaction fixes O2 instead of CO2. The energetic cost of oxygenation led to the evolution of C4 photosynthesis. In almost all C4 leaves compartmentation of photosynthesis between cells reduces oxygenation and so increases photosynthetic efficiency. Here we report that spatial expression of most C4 genes is controlled by intragenic cis-elements rather than promoter sequence. Two DNA motifs that cooperatively specify the patterning of genes required for C4 photosynthesis are identified. They are conserved in plants and algae that use the ancestral C3 pathway. As these motifs are located in exons they represent duons determining both gene expression and amino acid sequence. Our findings provide functional evidence for the importance of transcription factors recognising coding sequence as previously defined by genome-wide binding studies. Furthermore, they indicate that C4 evolution is based on ancient DNA motifs found in exonic sequence.

plant biology↗