Arabidopsis REF6 is a histone H3 lysine 27 demethylase

Xiaofeng Cao and colleagues report that REF6 is a histone H3 lysine 27 demethylase in Arabidopsis. REF6 demethylates H3K27me3 and H3K27me2 and ref6 mutant plants resemble mutations in H3K27me3-mediated gene silencing. Polycomb group (PcG)-mediated histone H3 lysine 27 trimethylation (H3K27me3) has a key role in gene repression and developmental regulation1,2,3,4. There is evidence that H3K27me3 is actively removed in plants5,6,7,8, but it is not known how this occurs. Here we show that RELATIVE OF EARLY FLOWERING 6 (REF6), also known as Jumonji domain–containing protein 12 (JMJ12), specifically demethylates H3K27me3 and H3K27me2, whereas its metazoan counterparts, the KDM4 proteins, are H3K9 and H3K36 demethylases9,10. Plants overexpressing REF6 resembled mutants defective in H3K27me3-mediated gene silencing. Genetic interaction tests indicated that REF6 acts downstream of H3K27me3 methyltransferases. Mutations in REF6 caused ectopic and increased H3K27me3 level and decreased mRNA expression of hundreds of genes involved in regulating developmental patterning and responses to various stimuli. Our work shows that plants and metazoans use conserved mechanisms to regulate H3K27me3 dynamics but use distinct subfamilies of enzymes.