Arabidopsis O‐GlcNAc transferase SEC activates histone methyltransferase ATX1 to regulate flowering

Post‐translational modification of proteins by O ‐linked β‐ N ‐acetylglucosamine ( O ‐GlcNAc) is catalyzed by O ‐GlcNAc transferases (OGTs). O ‐GlcNAc modification of proteins regulates multiple important biological processes in metazoans. However, whether protein O ‐GlcNAcylation is involved in epigenetic processes during plant development is largely unknown. Here, we show that loss of function of SECRET AGENT (SEC), an OGT in Arabidopsis , leads to an early flowering phenotype. This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C ( FLC ) locus, which encodes a key negative regulator of flowering. SEC activates ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT), through O ‐GlcNAc modification to augment ATX1‐mediated H3K4me3 histone modification at FLC locus. SEC transfers an O ‐GlcNAc group on Ser947 of ATX1, which resides in the SET domain, thereby activating ATX1. Taken together, these results uncover a novel post‐translational O ‐GlcNAc modification‐mediated mechanism for regulation of HKMT activity and establish the function of O ‐GlcNAc signaling in epigenetic processes in plants. Synopsis The Arabidopsis O ‐GlcNAc transferase SECRET AGENT (SEC) activates histone methyltransferase ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1) by O ‐GlcNAc modification, thereby instructing epigenetic modifications required for timely flowering. Arabidopsis mutant for O ‐GlcNAc transferase SEC exhibits an early flowering phenotype. Histone methyltransferase ATX1 is a substrate of SEC. SEC activates ATX1 through O ‐GlcNAcylation at serine 947. ATX1 epigenetically upregulates transcription of FLC, an inhibitor of flowering. Graphical Abstract Post‐translational regulation of a trithorax‐family methyltransferase by O ‐glycosylation reveals the involvement of O ‐GlcNAc signaling in epigenetic processes in plants.