Williams LAB @ UC Berkeley

1. What is epigenetics & how does it work?

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Epigenetics is the study of heritable information that is not contained within the DNA sequence of the genome. One example of this is DNA methylation - a reversible chemical modification to DNA that can be added or removed by specialized enzymes. DNA methylation can profoundly affect how a DNA sequence functions. Two genes with identical sequences can produce very different traits, depending on whether or not methylation is added to the DNA. Below is an example of a gene that changes the leaf surface when its DNA methylation is removed:

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In the Williams lab, we are interested in understanding how this epigenetic information is regulated and maintained by cells:

• How do the enzymes that add and remove DNA methylation find which sequences to act upon with precision?

• How do DNA methylation patterns get accurately inherited over many generations?

• How do these mechanisms function during the development of tissues and organs?

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2. Epigenetic dynamics during plant aging

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Key paper: Dai D, Chen K, Tao J, Williams BP. (2026). Aging drives a program of DNA methylation decay in plant organs. Science 391 (6784).​ 

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In humans, DNA methylation is one of the strongest molecular predictors of a person's age. In fact, DNA methylation may reflect true biological age more accurately than calendar age or a person's date of birth. In the Williams lab, we are working to define which dynamic changes to DNA methylation are reflected in the aging of tissues and organs of plants. We have found that despite its short lifespan, the model plant Arabidopsis displays remarkable patterns of epigenetic decay during leaf aging. 

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We have also found that the rate of epigenetic decay reflects rates of biological aging, for example in plants grown in short day conditions, or in fast/slow aging mutants. 

Currently, the lab is exploring the mechanisms behind two conditions in which plants don't show epigenetic aging that correlates with their age:
 

1) Meristems: the stem cells that make up plant meristems appear to show no changes to DNA methylation during aging, suggesting that these stem cells possess unique regulation of epigenetic integrity.

2) tcx5/tcx6 mutants: mutants of two genes, TCX5 and TCX6 (homologs of LIN54 in humans) show a complete absence of epigenetic decay during organ aging, despite the fact they show the same physical aging phenotypes as non-mutant plants. 

 

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3. How does epigenetics influence cell identity and regeneration?

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Key paper: Smoot NK, Zeng Y, Hochman RM, Williams BP (2026). DNA demethylation suppresses a state of enhanced cellular pluripotency and regeneration competence in Arabidopsis. bioRxiv https://doi.org/10.64898/2026.03.27.714943

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Every cell within an organism contains the same genome sequence, yet cells can differentiate into diverse and specialized cell types. The cells of many plant species show an extraordinary ability to be flexible, reversing or changing their specialized cell identity in response to certain conditions, such as the application of plant hormones. In the Williams lab, we are fascinated by how this happens at the level of perceiving and processing genetic and epigenetic information. 

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Our first progress in the area came with the discovery that mutants of the DNA demethylase pathway (such as the quadruple mutant drdd) regenerate roots and shoots from cuttings more efficiently than normal plants. This is a potentially important finding, as regenerating roots and shoots via tissue culture is currently a major bottleneck to crop improvement worldwide. 
 

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Above: leaves of WT and DNA demethylase mutant (dme, rdd, drdd) plants regenerating from root cuttings in tissue culture

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To our surprise, we even found that drdd mutants will regenerate roots and shoots without the plant hormones typically used in tissue culture. This is similar to many houseplants horticultural species, which can be propagated from cuttings. The lab is currently working on unpacking the precise mechanism through which DNA demethylases can regulate pluripotency and regeneration pathways. 

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Above: leaf cuttings of drdd mutants regenerating a root (left) and shoots (right)​