Findings surrounding the epigenetic inheritance that takes place in plants may have implications for agriculture, food supplies, and the environment. Now, new research has uncovered a key mechanism in chromatin remodeling in Arabidopsis. The findings show that, DECREASE in DNA METHYLATION 1 (DDM1) promotes replacement of histone variant H3.3 by H3.1 in heterochromatin and that H3.3 deposition prevents DNA methylation of heterochromatin in ddm1 mutants.

This research is published in Cell in the paper, “Chromatin remodeling of histone H3 variants by DDM1 underlies epigenetic inheritance of DNA methylation.”

Rob Martienssen, PhD, and Leemor Joshua-Tor, PhD, both professors at Cold Spring Harbor Laboratory (CSHL) and HHMI investigators, have been researching how plants pass along the markers that keep transposons inactive. One way to silence transposons, and protect the genome, is through methylation.

Martienssen and Joshua-Tor now show how protein DDM1 remodeling promotes the deposition of H3.1 H2A.W and DNA methylation. Plant cells need DDM1 because their DNA is tightly packaged. “But that blocks access to the DNA for all sorts of important enzymes,” Martienssen explained. Before methylation can occur, “you have to remove or slide the histones out of the way.”

Martienssen, together with former CSHL colleague Eric Richards, PhD, who is now a professor at the Boyce Thompson Institute, first discovered DDM1 30 years ago. Martienssen likens the protein’s movement to a yo-yo gliding along a string. The histones “can move up and down the DNA, exposing parts of the DNA at a time, but never falling off,” he explained.

This cartoon model illustrates, for the first time, where and how the DDM1 protein (purple) grips onto DNA (beige) during cell division.
[Joshua-Tor lab/Cryo-EM Facility/Cold Spring Harbor Laboratory]
Here, Martienssen and colleagues pinpointed the exact histones displaced by DDM1. Joshua-Tor used cryo-EM to capture detailed images of the enzyme interacting with DNA and associated proteins. They were able to show how DDM1 grabs onto particular histones to remodel packaged DNA. More specifically, the cryo-EM structure revealed contacts with variant H3 residues and deacetylated H4 tails. “An unexpected bond that ties DDM1 together turned out to correspond to the first mutation found all those years ago,” Joshua-Tor said.

The experiments also revealed how DDM1’s affinity for certain histones preserves epigenetic controls across generations. The team showed that a histone found only in pollen is resistant to DDM1 and acts as a placeholder during cell division. “It remembers where the histone was during plant development and retains that memory into the next generation,” Martienssen said.

Plants may not be alone here. Humans also depend on DDM1-like proteins to maintain DNA methylation. The new discovery may help explain how those proteins keep our genomes functional and intact.

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