The histone demethylase JMJD2A/KDM4A links ribosomal RNA transcription to nutrients and growth factors availability

• Published in: Nature communications Vol. 7; no. 1; p. 10174
• Main Authors: Salifou, Kader, Ray, Swagat, Verrier, Laure, Aguirrebengoa, Marion, Trouche, Didier, Panov, Konstantin I., Vandromme, Marie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05-01-2016; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/109; 13/89; 14/19; 38/15; 38/39; 38/71; 38/90; 631/337/176; 631/337/572; 631/80/86; 82/29; 96/1; Cell Line, Tumor; DNA, Ribosomal - genetics; DNA, Ribosomal - metabolism; Gene Expression Regulation - physiology; Histones - metabolism; Humanities and Social Sciences; Humans; Jumonji Domain-Containing Histone Demethylases - genetics; Jumonji Domain-Containing Histone Demethylases - metabolism; Mitogen-Activated Protein Kinase Kinases - genetics; Mitogen-Activated Protein Kinase Kinases - metabolism; multidisciplinary; Protein Transport; RNA, Ribosomal - genetics; RNA, Ribosomal - metabolism; Science; Science (multidisciplinary); TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; Transcription, Genetic - physiology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10174

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.
Histone methylation regulates gene expression. Here, Salifou
et al.
show that KDM4A, a histone lysine demethylase, regulates RNA polymerase I-driven transcription in a PI3K dependent manner, therefore linking nutrients and growth factors availability to ribosomal RNA transcription.