Histone methyltransferase TXR1 is required for both H3 and H3.3 lysine 27 methylation in the well-known ciliated protist Tetrahymena thermophila

DNA replication elongation is tightly controlled by histone-modifying enzymes. Our previous studies showed that the histone methytransferase TXR1 (Tetrahymena Trithorax related protein 1) specifically catalyzes H3K27 monomethylation and affects DNA replication elongation in Tetrahymena thermophila. In this study, we investigated whether TXR1 has a substrate preference to the canonical H3 over the replacement variant H3.3. We demonstrated by histone mutagenesis that K27Q mutation in H3.3 further aggravated the replication stress phenotype of K27Q mutation in canonical H3, supporting H3.3 as a physiologically relevant substrate of TXR1. This result is in apparent contrast to the strong preference for canonical H3 recently reported in Arabidopsis homologues ATXR5 and ATXR6, and further corroborates the role of TXR1 in DNA replication.