title: The histone demethylase JMJD2A/KDM4A links ribosomal RNA transcription to nutrients and growth factors availability.
abstract: The interplay between methylation and demethylation of histone lysine residues is an essential component of gene expression regulation and there is considerable interest in elucidating the roles of proteins involved. Here we report that histone demethylase KDM4A/JMJD2A, which is involved in the regulation of cell proliferation and is overexpressed in some cancers, interacts with RNA Polymerase I, associates with active ribosomal RNA genes and is required for serum-induced activation of rDNA transcription. We propose that KDM4A controls the initial stages of transition from 'poised', non-transcribed rDNA chromatin into its active form. We show that PI3K, a major signalling transducer central for cell proliferation and survival, controls cellular localization of KDM4A and consequently its association with ribosomal DNA through the SGK1 downstream kinase. We propose that the interplay between PI3K/SGK1 signalling cascade and KDM4A constitutes a mechanism by which cells adapt ribosome biogenesis level to the availability of growth factors and nutrients.
authors.affiliation: Centre for Integrative Biology, Université de Toulouse, UT3 Toulouse, France.|Centre for Integrative Biology, CNRS, UT3 Toulouse, France.
authors.forename: Kader
authors.initials: K
authors.lastname: Salifou
authors.affiliation: School of Biological Sciences, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: Swagat
authors.initials: S
authors.lastname: Ray
authors.affiliation: Centre for Integrative Biology, Université de Toulouse, UT3 Toulouse, France.|Centre for Integrative Biology, CNRS, UT3 Toulouse, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Verrier
authors.affiliation: Centre for Integrative Biology, Université de Toulouse, UT3 Toulouse, France.|Centre for Integrative Biology, CNRS, UT3 Toulouse, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Aguirrebengoa
authors.affiliation: Centre for Integrative Biology, Université de Toulouse, UT3 Toulouse, France.|Centre for Integrative Biology, CNRS, UT3 Toulouse, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Trouche
authors.affiliation: School of Biological Sciences, Queen's University Belfast, Belfast BT9 7BL, UK.|Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast BT9 7AE, UK.
authors.forename: Konstantin I
authors.initials: KI
authors.lastname: Panov
authors.affiliation: Centre for Integrative Biology, Université de Toulouse, UT3 Toulouse, France.|Centre for Integrative Biology, CNRS, UT3 Toulouse, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Vandromme
mesh_terms: D045744:Cell Line, Tumor; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D004275:DNA, Ribosomal; D006657:Histones; D012335:RNA, Ribosomal; D056484:Jumonji Domain-Containing Histone Demethylases; C494424:KDM4A protein, human; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases