Lopez-Bigas Nuria, Kisiel Tomasz A, DeWaal Dannielle C, Holmes Katie B, Volkert Tom L, Gupta Sumeet, Love Jennifer, Murray Heather L, Young Richard A, Benevolenskaya Elizaveta V
Research Unit on Biomedical Informatics, Experimental and Health Science Department, Universitat Pompeu Fabra, Barcelona 08080, Spain.
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 900 South Ashland Avenue, Chicago, IL 60607, USA.
Mol Cell. 2008 Aug 22;31(4):520-530. doi: 10.1016/j.molcel.2008.08.004.
Retinoblastoma protein (pRB) mediates cell-cycle withdrawal and differentiation by interacting with a variety of proteins. RB-Binding Protein 2 (RBP2) has been shown to be a key effector. We sought to determine transcriptional regulation by RBP2 genome-wide by using location analysis and gene expression profiling experiments. We describe that RBP2 shows high correlation with the presence of H3K4me3 and its target genes are separated into two functionally distinct classes: differentiation-independent and differentiation-dependent genes. The former class is enriched by genes that encode mitochondrial proteins, while the latter is represented by cell-cycle genes. We demonstrate the role of RBP2 in mitochondrial biogenesis, which involves regulation of H3K4me3-modified nucleosomes. Analysis of expression changes upon RBP2 depletion depicted genes with a signature of differentiation control, analogous to the changes seen upon reintroduction of pRB. We conclude that, during differentiation, RBP2 exerts inhibitory effects on multiple genes through direct interaction with their promoters.
视网膜母细胞瘤蛋白（pRB）通过与多种蛋白质相互作用来介导细胞周期停滞和分化。RB结合蛋白2（RBP2）已被证明是一个关键效应因子。我们试图通过定位分析和基因表达谱实验在全基因组范围内确定RBP2的转录调控作用。我们发现RBP2与H3K4me3的存在高度相关，并且其靶基因可分为两个功能不同的类别：不依赖分化的基因和依赖分化的基因。前一类基因富含编码线粒体蛋白的基因，而后一类基因则以细胞周期基因为主。我们证明了RBP2在线粒体生物发生中的作用，这涉及对H3K4me3修饰核小体的调控。对RBP2缺失后表达变化的分析显示出具有分化控制特征的基因，类似于重新引入pRB时所观察到的变化。我们得出结论，在分化过程中，RBP2通过与其启动子直接相互作用对多个基因发挥抑制作用。
