Chaperone Proteins: Bridging Protein Accumulation with Epigenetic Mechanisms and Gene Regulation in Arabidopsis thaliana
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Chaperone Proteins: Bridging Protein Accumulation with Epigenetic Mechanisms and Gene Regulation in Arabidopsis thaliana

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Abstract

DNA methylation has been studied for decades and is necessary to maintain cellular homeostasis from humans to plants. However, there remains a dearth of information regarding the function of proteins that bind DNA methylation. It remains unclear if plant DNA methylation binding proteins bind DNA methylation, which methylation sequence context (CG, CHG, or CHH) they prefer, or how these proteins interpret DNA methylation to regulate gene or transposable element (TE) expression. Therefore, we studied the methyl-CpG-binding domain (MBD) protein family in Arabidopsis thaliana to expand on the mechanisms of DNA methylation-mediated gene regulation. We discovered that Arabidopsis MBD proteins MBD5 and MBD6 redundantly regulate the expression of promoter-methylated genes and TEs by recruiting chaperone proteins ACD15, ACD21, and SLN. We further discovered that the MBD5/6 complex co-opts the oligomerization capacity of small heat shock proteins (sHSPs), ACD15 and ACD21, to accumulate the MBD5/6 complex at sites of high-density methylation creating nuclear foci which are further regulated by SLN. Although chaperone proteins often interact with bound complexes, the surprising specificity with which ACD15, ACD21, and SLN directly regulate the MBD5/6 complex is novel and unprecedented for DNA methylation binding proteins. Furthermore, proper accumulation is necessary for gene regulation by the MBD5/6 complex suggesting protein accumulation at DNA methylation sites is an integral step in DNA methylation-mediated gene regulation in plants. Our results suggest this chaperone-mediated accumulation is not specific to Arabidopsis proteins as protein accumulation was caused by sHSPs from other organisms including humans, archaea, bacteria, protists, and other plant species. Using a chimeric protein approach, we show that MBD6 foci can be replicated using these sHSPs, in an ACD15/ACD21 independent manner, leading to subtle gene silencing. We further demonstrate chaperone-mediated accumulation using these sHSPs by targeting specific genomic loci using the SunTag, dCa9 targeting system. These results support the role of protein accumulation in DNA methylation pathways while providing novel mechanisms for protein localization in chromatin environments. Evidence is growing that efficient protein accumulation and localization are important for the function of chromatin complexes. The discovery of phase separation events and membrane-less compartments has led to a reevaluation of how protein dynamics can impact chromatin function through novel and potentially overlooked mechanisms. Our work has added to this evidence by demonstrating that plants utilize chaperone proteins to efficiently and specifically accumulate DNA methylation-binding proteins, forming an organized and functional accumulation.

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This item is under embargo until May 28, 2026.