Salifou Kader, Ray Swagat, Verrier Laure, Aguirrebengoa Marion, Trouche Didier, Panov Konstantin I, Vandromme Marie
Centre for Integrative Biology, Université de Toulouse, UT3 Toulouse, France.
Centre for Integrative Biology, CNRS, UT3 Toulouse, France.
Nat Commun. 2016 Jan 5;7:10174. 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.
组蛋白赖氨酸残基的甲基化与去甲基化之间的相互作用是基因表达调控的重要组成部分，人们对阐明相关蛋白质的作用有着浓厚兴趣。在此我们报告，参与细胞增殖调控且在某些癌症中过表达的组蛋白去甲基化酶KDM4A/JMJD2A与RNA聚合酶I相互作用，与活跃的核糖体RNA基因相关联，并且是血清诱导的rDNA转录激活所必需的。我们提出，KDM4A控制着从“ poised”的非转录rDNA染色质转变为其活跃形式的初始阶段。我们表明，PI3K是细胞增殖和存活的主要信号转导分子，它通过SGK1下游激酶控制KDM4A的细胞定位，从而控制其与核糖体DNA的关联。我们提出，PI3K/SGK1信号级联与KDM4A之间的相互作用构成了一种机制，通过该机制细胞可使核糖体生物合成水平适应生长因子和营养物质的可利用性。
