Control of histone demethylation by nuclear-localized α-ketoglutarate dehydrogenase

Methylations on nucleosomal histones play fundamental roles in regulating eukaryotic transcription. Jumonji C domain-containing histone demethylases (JMJs) dynamically control the level of histone methylations. However, how JMJ activity is generally regulated is unknown. We found that the tricarboxylic acid cycle-associated enzyme α-ketoglutarate (α-KG) dehydrogenase (KGDH) entered the nucleus, where it interacted with various JMJs to regulate α-KG-dependent histone demethylations by JMJs, and thus controlled genome-wide gene expression in plants. We show that nuclear targeting is regulated by environmental signals and that KGDH is enriched at thousands of loci in Arabidopsis thaliana. Chromatin-bound KGDH catalyzes α-KG decarboxylation and thus may limit its local availability to KGDH-coupled JMJs, inhibiting histone demethylation. Thus, our results uncover a regulatory mechanism for histone demethylations by JMJs.