ATX3, ATX4, and ATX5 Encode Putative H3K4 Methyltransferases and Are Critical for Plant Development

Methylation of Lys residues in the tail of the H3 histone is a key regulator of chromatin state and gene expression, conferred by a large family of enzymes containing an evolutionarily conserved SET domain. One of the main types of SET domain proteins are those controlling H3K4 di- and trimethylation. The genome of Arabidopsis (Arabidopsis thaliana) encodes 12 such proteins, including five ARABIDOPSIS TRITHORAX (ATX) proteins and seven ATX-Related proteins. Here, we examined three until-now-unexplored ATX proteins, ATX3, ATX4, and ATX5. We found that they exhibit similar domain structures and expression patterns and are redundantly required for vegetative and reproductive development. Concurrent disruption of the ATX3, ATX4, and ATX5 genes caused marked reduction in H3K4me2 and H3K4me3 levels genome-wide and resulted in thousands of genes expressed ectopically. Furthermore, atx3/atx4/atx5 triple mutants resulted in exaggerated phenotypes when combined with the atx2 mutant but not with atx1. Together, we conclude that ATX3, ATX4, and ATX5 are redundantly required for H3K4 di- and trimethylation at thousands of sites located across the genome, and genomic features associated with targeted regions are different from the ATXR3/SDG2-controlled sites in Arabidopsis.