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表观遗传调控的网络生物学方法

A network biology approach to epigenetic regulation
课程网址: http://videolectures.net/ESHGsymposium2016_valencia_network_biolo...  
主讲教师: Alfonso Valencia
开课单位: 西班牙国家癌症研究中心
开课时间: 2016-07-28
课程语种: 英语
中文简介:
将分子系统描述为网络,这为使用从社会学到神经学等其他领域的网络分析方法提供了可能。在这种情况下,我们分析了小鼠胚胎干细胞(mESC)在不同组织水平的表观遗传修饰的特性。mESC是目前最具特色的表观遗传学系统,包括许多基本成分的数据:染色质相关蛋白(CRP)、组蛋白修饰、DNA甲基化修饰、大量蛋白质和修饰的基因组作图偏好(芯片序列数据)和细胞核中染色质的组织,通过染色质捕获实验确定。 我们对这些异质的“mESC表观遗传特性”进行了处理,构建了一个由crp、组蛋白标记和DNA修饰组成的综合网络,这些修饰由它们在基因组中共同定位的倾向联系在一起。在这个网络中,共定位偏好是特定于“mESC染色质状态”的,例如启动子和增强子。对“共定位”网络性质的分析表明,其中一个DNA修饰5hmC是该网络组织的关键组成部分。通过对网络中蛋白质组分的进化分析,证实了5hmC在网络中的重要性,其中5hmC在mESC网络的蛋白质组分协同进化中起中介作用。 我们进一步探讨了“mESC表观遗传特性”和“mESC染色质状态”在最终控制基因表达的细胞核结构背景下的功能意义。研究结果揭示了mESC表观遗传控制系统的有趣结构特性,与新出现的基因表达控制和染色质组织模型一致。在方法论层面,我将介绍网络分析方法在探索复杂生物系统的功能和进化特性方面日益重要。
课程简介: The description of molecular systems as networks opens the possibility of using all the methodology developed for network analysis in other fields from sociology to neurology. In this case, we have analysed the properties of Mouse Embryonic Stem Cells (mESC) at different levels of the organization of epigenetic modifications. mESC is currently the best characterised epigenetics system, including data on many of the basic components: Chromatin Related Proteins (CRPs), Histone modifications, DNA methylation modifications, the genome mapping preferences of a large collection of proteins and modifications (ChIP-Seq data) and organization of the chromatin in the nucleus, determined with Chromatin Capture Experiments. We have processed these heterogeneous “mESC Epigenetic Properties” to build a comprehensive network of CRPs, histone marks and DNA modifications linked by their propensity to co-localize in the genome. In this network co-localization preferences are specific of “mESC Chromatin States”, such as Promoters and Enhancers. The analysis of the properties of the “co-localization” network points to one of the DNA modifications 5hmC as the key component in the organization of this network. The importance of 5hmC in the network is reinforced by the evolutionary analysis of the protein components of the network, in which 5hmC acts as a mediator in the co-evolution of the protein components of the mESC network. We have further explored the functional significance of the “mESC Epigenetic Properties” and “mESC Chromatin States” by analysing them in the context of the structure of the nucleus that ultimately controls genes expression. The results revealed interesting properties of the organization of the mESC epigenetic control system, in line with the emerging models of gene expression control and chromatin organization. At the methodological level, I will introduce the growing importance of Network analysis methodology in the exploration of the functional and evolutionary properties of complex biological systems.
关 键 词: 基因; 遗传学; 染色质
课程来源: 视频讲座网
数据采集: 2020-12-14:yxd
最后编审: 2020-12-14:yxd
阅读次数: 51