A plant histone H3.3-specific amino acid safeguards the deposition of H3K36 methylation for proper plant development and stress responses [G34]
Histone variants are critical determinants for chromatin function with diverse regulatory mechanisms. The H3 variants, H3.1 and H3.3, evolved independently in animals and plants. A significant difference between H3.1 and H3.3 is the amino acid variation at position 31, with H3.1 carrying alanine (A), while H3.3 bearing serine (S) in animals or threonine (T) in plants. Both S and T can be phosphorylated, but why plants have selectively adopted T over S remains unclear. Here, we report the specific role of plant H3.3T31 in controlling plant development and stress responses by promoting the deposition of histone H3 lysine 36 trimethylation (H3K36me3) on H3.3. T31 prevents plant-specific H3K27 methyltransferases, ATXR5 and ATXR6, from depositing H3K27 monomethylation (H3K27me1), which inhibits the activity of H3K36 methyltransferase EFS. Substituting H3.3T31 with an S or A residue results in increased ATXR5/6 activity and elevated H3K27me1 levels, leading to a reduction in H3K36me3. Moreover, we show that unlike H3.3 T31S and T31A mutations, cancer-associated G34R and G34W mutations directly disrupt H3K36me3 deposition without affecting H3K27me1. These G34 mutations may also influence H3.3 function through mechanisms beyond the disruption of H3K36me3. Our data suggest a co-evolution of the plant-specific H3.3T31 residue and H3K27 methyltransferases ATXR5/6, which ensures the selective accumulation of H3K27me1 on H3.1 and H3K36me3 on H3.3, thereby enabling proper chromatin function. Overall design: To examine transcriptomic changes in h3.3ko;HTR5 G34R, h3.3ko;HTR5 G34W