MBD8 acts as a conserved cofactor of the histone demethylase LDL2 to regulate flowering time in plants

Histone demethylases have been extensively characterized in plants, yet how their enzymatic activities are regulated remains largely unknown. Here, we identify that MBD8, a protein harboring a putative methyl-CpG-binding domain (MBD), forms a protein complex with the histone demethylase LDL2 in Arabidopsis thaliana. In this complex, MBD8 functions as a cofactor that is required for efficient LDL2-mediated removal of mono- and di-methylation at histone H3 (H3K4me1 and H3K4me2) across the genome. In the Arabidopsis C24 ecotype, loss-of-function mutations in MBD8 and LDL2 result in indistinguishable late-flowering phenotypes, which are consistent with increased enrichment of H3K4me1 and H3K4me2 at the flowering repressor loci MAF1 and MAF5. Importantly, we demonstrate that the rice (Oryza sativa) MBD8 orthologs MBD708, MBD709, and MBD715 also interact with the LDL2 ortholog Hd18 to form a protein complex, and disruption of these components delays flowering by reprogramming the expression of genes associated with floral transition. Collectively, this study reveals an evolutionarily conserved mechanism in which MBD8 orthologs act as cofactors of LDL2 orthologs to regulate histone demethylation and flowering time in plants.