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bioRxiv · 10.1101/2025.09.03.673934

Major alleles of CDCA7α shape CG-methylation in Arabidopsis thaliana

Bourguet, P.·Lorkovic, Z. J.·Casado, D. K.·Bapteste, V.·Cho, C. H.·Igolkina, A.·Lee, C.-R.·Nordborg, M.·Berger, F.·Sasaki, E.
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Abstract

DNA methylation is a key epigenetic mark that impacts gene expression and represses transposable elements (TEs) in eukaryotes. Numerous examples of cis-elements targeted by DNA methylation, particularly at CG sites (mCG), have been reported to be under selective pressure in animals and plants. By contrast, there is limited knowledge of trans-regulators of mCG leading to adaptation. Here, using genome-wide association studies, we identify CELL DIVISION CYCLE-ASSOCIATED PROTEIN 7 ALPHA (CDCA7) as a trans-regulator of mCG in natural populations of Arabidopsis thaliana. CDCA7 and its paralog, CDCA7{beta}, directly bind to the chromatin remodeler DECREASE IN DNA METHYLATION 1 (DDM1), which facilitates access of methyltransferases to DNA. CDCA7/{beta} selectively regulates mCG and minimally impacts other DDM1-dependent processes such as non-CG methylation and histone variant deposition. We identify the cis-regulatory sequence modulating CDCA7 expression in natural populations and determining the degree of mCG and TE silencing. The geographic distribution of CDCA7 alleles suggests that new alleles have repeatedly expanded to novel ecological niches, indicating a potential role in local adaptation. Altogether, our findings provide new insight into how changes in global DNA methylation levels through transcriptional regulation of the epigenetic machinery have the capacity to facilitate local adaptation.

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Bourguet, P., Lorkovic, Z. J., Casado, D. K., Bapteste, V., Cho, C. H., Igolkina, A., Lee, C.-R., Nordborg, M., Berger, F., Sasaki, E.. 2025-09-07. Major alleles of CDCA7α shape CG-methylation in Arabidopsis thaliana. https://doi.org/10.1101/2025.09.03.673934

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