Li Luolan, Lorzadeh Alireza, Hirst Martin
Centre for High-Throughput Biology, Department of Microbiology & Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
Wiley Interdiscip Rev Syst Biol Med. 2014 Jan-Feb;6(1):37-59. doi: 10.1002/wsbm.1250. Epub 2013 Nov 19.
Transcriptional regulation involves complex and interdependent interactions of noncoding and coding regions of the genome with proteins that interact and modify them. Genetic variation/mutation in coding and noncoding regions of the genome can drive aberrant transcription and disease. In spite of accounting for nearly 98% of the genome comparatively little is known about the contribution of noncoding DNA elements to disease. Genome-wide association studies of complex human diseases including cancer have revealed enrichment for variants in the noncoding genome. A striking finding of recent cancer genome re-sequencing efforts has been the previously underappreciated frequency of mutations in epigenetic modifiers across a wide range of cancer types. Taken together these results point to the importance of dysregulation in transcriptional regulatory control in genesis of cancer. Powered by recent technological advancements in functional genomic profiling, exploration of normal and transformed regulatory networks will provide novel insight into the initiation and progression of cancer and open new windows to future prognostic and diagnostic tools.
转录调控涉及基因组中非编码区和编码区与相互作用并对其进行修饰的蛋白质之间复杂且相互依存的相互作用。基因组编码区和非编码区的遗传变异/突变可导致异常转录和疾病。尽管非编码DNA元件占基因组近98%，但人们对其在疾病中的作用了解相对较少。包括癌症在内的复杂人类疾病的全基因组关联研究已揭示非编码基因组中变异的富集。近期癌症基因组重测序工作的一个惊人发现是，在广泛的癌症类型中，表观遗传修饰因子的突变频率此前未得到充分重视。综合这些结果表明，转录调控失控在癌症发生中具有重要意义。借助功能基因组图谱分析的最新技术进展，对正常和转化的调控网络进行探索将为癌症的发生和发展提供新的见解，并为未来的预后和诊断工具打开新的窗口。
