Le Guezennec Xavier, Brinkman Arie B, Vermeulen Michiel, Denissov Sergeï G, Gazziola Cinzia, Lohrum Marion E, Stunnenberg Henk G
Nijmegen Center for Molecular Life Sciences, Department of Molecular Biology, Radboud University Nijmegen, Geert Grooteplein 30, Nijmegen, the Netherlands.
BJU Int. 2005 Dec;96 Suppl 2:16-22. doi: 10.1111/j.1464-410X.2005.05942.x.
Despite the availability of several completely sequenced genomes, we are still, for the most part, ignorant about how genes interact and regulate each other within a given cell type to specify identity, function and cellular memory. A realistic model of cellular regulation based on current knowledge indicates that many interacting networks operate at the epigenetic, transcriptional, translational and post-translational levels, with feedback between the various levels. Protein-protein and protein-DNA interactions help to define which genes may be activated in a particular cell, and determine whether external cues cause activation or repression. New technologies, e.g. proteomics using mass spectrometry, high-density DNA or oligonucleotide microarrays (chips), and chromatin immunoprecipitation (ChIP), provide new and exciting tools for deciphering the pathways and proteins controlling gene expression. Analysis of these pathways offers new insight that aids targeted drug development.
尽管已有多个全序列基因组可供使用,但在很大程度上,我们仍然不清楚基因在给定细胞类型中如何相互作用和相互调节,以确定细胞身份、功能和细胞记忆。基于当前知识的细胞调控现实模型表明,许多相互作用的网络在表观遗传、转录、翻译和翻译后水平上运行,各水平之间存在反馈。蛋白质-蛋白质和蛋白质-DNA相互作用有助于确定哪些基因可能在特定细胞中被激活,并确定外部信号是导致激活还是抑制。新技术,如使用质谱的蛋白质组学、高密度DNA或寡核苷酸微阵列(芯片)以及染色质免疫沉淀(ChIP),为破译控制基因表达的途径和蛋白质提供了新的、令人兴奋的工具。对这些途径的分析提供了有助于靶向药物开发的新见解。