title: CxxC-ZF domain is needed for KDM2A to demethylate histone in rDNA promoter in response to starvation.
abstract: The transcription of ribosomal RNA genes (rDNA) is a rate-limiting step in ribosome biogenesis and changes profoundly in response to environmental conditions. Recently we reported that JmjC demethylase KDM2A reduces rDNA transcription on starvation, with accompanying demethylation of dimethylated Lys 36 of histone H3 (H3K36me2) in rDNA promoter. Here, we characterized the functions of two domains of KDM2A, JmjC and CxxC-ZF domains. After knockdown of endogenous KDM2A, KDM2A was exogenously expressed. The exogenous wild-type KDM2A demethylated H3K36me2 in the rDNA promoter on starvation and reduced rDNA transcription as endogenous KDM2A. The exogenous KDM2A with a mutation in the JmjC domain lost the demethylase activity and did not reduce rDNA transcription on starvation, showing that the demethylase activity of KDM2A itself is required for the control of rDNA transcription. The exogenous KDM2A with a mutation in the CxxC-ZF domain retained the demethylase activity but did not reduce rDNA transcription on starvation. It was found that the CxxC-ZF domain of KDM2A bound to the rDNA promoter with unmethylated CpG dinucleotides in vitro and in vivo. The exogenous KDM2A with the mutation in the CxxC-ZF domain failed to reduce H3K36me2 in the rDNA promoter on starvation. Further, it was suggested that KDM2A that bound to the rDNA promoter was activated on starvation. Our results demonstrate that KDM2A binds to the rDNA promoter with unmethylated CpG sequences via the CxxC-ZF domain, demethylates H3K36me2 in the rDNA promoter in response to starvation in a JmjC domain-dependent manner, and reduces rDNA transcription.
authors.affiliation: Laboratory of Molecular and Cellular Biology, Faculty of Pharmacy, Takasaki University of Health and Welfare.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Umata
authors.forename: Kengo
authors.initials: K
authors.lastname: Okamoto
authors.forename: Chikashi
authors.initials: C
authors.lastname: Obuse
authors.forename: Makoto
authors.initials: M
authors.lastname: Tsuneoka
mesh_terms: D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004275:DNA, Ribosomal / Q000235:genetics* / Q000378:metabolism; D044783:F-Box Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005508:Food Deprivation; D005947:Glucose / Q000378:metabolism; D006657:Histones / Q000235:genetics*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014158:Transcription, Genetic; D016335:Zinc Fingers
chemical_list: D004275:DNA, Ribosomal; D044783:F-Box Proteins; D006657:Histones; D056484:Jumonji Domain-Containing Histone Demethylases; C534524:KDM2A protein, human; D005947:Glucose