A comparative encyclopedia of DNA elements in the mouse genome

摘要

小鼠是生物医学研究中最好的模型生物。为了获得关于共同的和物种特定性的转录和细胞调控程序的更多信息,名为"Mouse ENCODE Consortium"的联合项目组在各种不同细胞和组织类型中对整个小鼠基因组内的转录、 DNase Ⅰ超敏性、转录因子结合、染色质修饰和复制域进行了分析标绘。这些发现被与人类的相应数据进行比较,从而证实在新注解的潜在功能序列中存在很大程度上的保守性,也揭示了在转录调控、染色质状态和高层次染色质组织中所涉及的其他序列的显著差异。这些数据和对它们所做的分析为研究哺乳动物生物学和人类疾病的机制提供了一个宝贵的资源。本期Wature发表了4篇来自该项目组的论文,另外在一篇News & Views文章中Piero Carninci 还对该项目组所获得的数据集将会怎样帮助我们了解人类生物学及生物医学问题进行了分析。%The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization. Our results illuminate the wide range of evolutionary forces acting on genes and their regulatory regions, and provide a general resource for research into mammalian biology and mechanisms of human diseases.