JmjC enzyme KDM2A is a regulator of rRNA transcription in response to starvation

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Abstract
The rate‐limiting step in ribosome biogenesis is the transcription of ribosomal RNA, which is controlled by environmental conditions. The JmjC enzyme KDM2A/JHDM1A/FbxL11 demethylates mono‐ and dimethylated Lys 36 of histone H3, but its function is unclear. Here, we show that KDM2A represses the transcription of ribosomal RNA. KDM2A was localized in nucleoli and bound to the ribosomal RNA gene promoter. Overexpression of KDM2A repressed the transcription of ribosomal RNA in a demethylase activity‐dependent manner. When ribosomal RNA transcription was reduced under starvation, a cell‐permeable succinate that inhibited the demethylase activity of KDM2A prevented the reduction of ribosomal RNA transcription. Starvation reduced the levels of mono‐ and dimethylated Lys 36 of histone H3 marks on the rDNA promoter, and treatment with the cell‐permeable succinate suppressed the reduction of the marks during starvation. The knockdown of KDM2A increased mono‐ and dimethylated Lys 36 of histone H3 marks, and suppressed the reduction of ribosomal RNA transcription under starvation. These results show a novel mechanism by which KDM2A activity is stimulated by starvation to reduce ribosomal RNA transcription.