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Elucidating gene regulation using plant model

Nature stops some genes from being expressed with small chemical modifications of the DNA and associated proteins that can be inherited. Scientists have shown in part how this works in a plant model system.
Elucidating gene regulation using plant model
Chromatin in plants and animals is nothing but DNA folded with histone and non-histone proteins. Some portions of the chromatin (heterochromatin) contain genes whose expression is largely silenced through the addition of methyl groups to histone proteins (methylation). The association of heterochromatin with DNA methylation is possibly due to nearby histone methylation. In fact, DNA methylation can persist over generations, resulting in heritable changes in gene expression without changes in DNA sequence (epigenetics).

The plant Arabidopsis thaliana shares with mammals a recently discovered group of proteins that has a methylated DNA-binding domain that could play a role in DNA methylation. This suggests that A. thaliana could be a model system for DNA methylation in mammals. Original plans to study this system with the EU-funded project SRA AND EPIGENETICS were modified as another research team published their results about this system. Research focus was then applied to study of heterochromatin formation and its relationship to replication-related phenotype of atxr5/6 mutants.

Perseverance and creativity on the part of the project researchers enabled an in-depth analysis of controls on DNA replication (that also inhibits DNA re-replication or replication more than once during a cell cycle). Plants with mutations in specific histone methyltransferases, enzymes mediating transfer of methyl groups to histone proteins, demonstrated localised re-replication in heterochromatin.

Heterochromatin in both plants and animals is generally characterised by the methylation of both DNA and histones of type H3K9. In A. thaliana, the methylation sites are co-located and mutually self-stabilising. Research revealed that this plant can adapt to extracellular cues by regulating gene expression and histone deposition independently of DNA methylation. Work resulted in a patent application. Further studies on the relationship between histone H3K9 dimethylation (H3K9me2) and DNA methylation revealed a distinct and novel interplay between the two.

SRA AND EPIGENETICS contributed ground-breaking work to the field of epigenetics with important publications in internationally recognised scientific journals. Better understanding of the complex mechanisms of gene expression could eventually be important to disease characterisation and the development of novel therapies.

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