Major alleles of CDCA7 shape CG methylation in Arabidopsis thaliana

DNA methylation is a key epigenetic mark that impacts gene expression and represses transposable elements 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, a genome-wide association study identifies CELL DIVISION CYCLE-ASSOCIATED PROTEIN 7 (CDCA7) as a major trans determinant of mCG in natural populations of Arabidopsis thaliana. CDCA7 or its paralogue physically binds the chromatin remodeller DECREASE IN DNA METHYLATION 1 (DDM1), which facilitates access of methyltransferases to DNA. Epigenomic analysis shows that while CDCA7 proteins control all DDM1-dependent processes, their predominant function is the maintenance of mCG. We identify a 26-bp promoter indel modulating CDCA7 expression in natural populations and determining the degree of mCG and transposable element 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. Our findings establish CDCA7 proteins as dedicated regulators of mCG and imply that DDM1 relies on alternative partners to regulate other chromatin features. Broadly, they illustrate how changes in global DNA methylation levels through transcriptional regulation of the epigenetic machinery have the capacity to facilitate local adaptation.