LAUSR

Cadmium (Cd) is a toxic metal that contributes to human diseases such as pediatric cancer and cardiovascular dysfunction. Epigenetic modification caused by Cd exposure is the major factor in etiology of environmentally-relevant diseases. However, the underlying epigenetic mechanism for Cd uptake and accumulation in food crops, particularly those growing in Cd-contaminated environments, is largely unknown. This study investigated uncharacterized regulatory mechanisms and biological functions of global DNA hypomethylation at CG sites that are associated with gene expression for Cd detoxification and accumulation in the food crop rice. Mutation of the CG maintenance enzyme OsMET1 confers rice tolerance to Cd exposure. Genome-wide analysis of OsMET1 loss of function mutant Osmet1 and its wild type shows numerous loci differentially methylated and upregulated genes for Cd detoxification, transport and accumulation. We functionally identified a new locus for a putative cadmium tolerance factor (here termed as OsCTF) and demonstrated that Cd-induced DNA demethylation is the drive of OsCTF expression. The 3'-UTR of OsCTF is the primary site of DNA and histone (H3K9me2) demethylation, which is associated with higher levels of OsCTF transcripts detected in the Osmet1 and Ossdg714 mutant lines. Mutation of OsCTF in rice led to hypersensitivity to Cd and the Osctf line accumulated more Cd, whereas transfer of OsCTF back to the Osctf mutant completely restored the normal phenotype. Our work unveiled an important epigenetic mechanism and will help develop breeding crops that contribute to food security and better human health.