Structure function and evolution of yeast transcription networks

描述（由申请人提供）：所有细胞不断调整其基因表达程序，以应对环境和遗传干扰。基因表达的变化是由一个复杂的调控网络介导的，其中转录调控是一个主要组成部分。细胞转录网络基本上调节所有生物过程，从发育到癌症和衰老。拟议研究的目标是开发新的理论和实验方法，以酵母为模式生物，系统地分析转录网络的结构，功能和进化。基于我们在上一个资助期取得的重大进展，我们将继续努力在基因组规模上重建酵母转录网络。为了理解网络结构的生理重要性，我们将定量分析基因组中所有转录因子的缺失突变体在各种条件下的生长表型，并将全局基因表达程序与细胞的适应性联系起来。我们将扩大我们的研究范围，纳入全基因组范围的核小体定位信息，以更好地了解核小体定位和转录调控之间的关系。我们将系统地对不同酵母物种中的转录电路进行比较分析，以得出控制其进化的基本原则。这些系统水平的研究将揭示基本的功能和进化的限制和设计原则的转录网络超越酵母系统。此外，由于许多生物过程是高度保守的，因此酵母中转录调控的特定知识可以转移到包括人类在内的高等真核生物中。 公共卫生相关性：细胞转录网络基本上调节所有生物过程，包括发育，癌症和衰老。这些过程的错误调节导致人类疾病。对酵母中转录网络的结构、功能和进化的全面了解可能会导致适用于人类的一般原则，并对人类健康产生重大影响。

DESCRIPTION (provided by applicant): All cells constantly adjust their gene expression programs in response to environmental and genetic perturbations. The changes in gene expression are mediated by a complex regulatory network, of which transcriptional regulation is a major component. Cellular transcription networks regulate essentially all biological processes, from development to cancer and aging. The goal of the proposed research is to develop novel theoretical and experimental approaches to systematically analyze the structure, function, and evolution of transcription networks, using yeast as a model organism. Building on the significant progress we have made in the previous granting period, we will continue our efforts to reconstruct yeast transcription networks at a genomic scale. To understand the physiological importance of the network structure, we will quantitatively analyze the growth phenotypes of the deletion mutants of all the transcription factors in the genome under a variety of conditions, and connect global gene expression program to the fitness of the cell. We will expand the scope of our study to incorporate genome- wide nucleosome positioning information, to better understand the relationship between nucleosome positioning and transcriptional regulation. We will systematically perform comparative analysis of transcriptional circuits in different yeast species, in order to derive basic principles governing their evolution. Together these systems-level studies will reveal the basic functional and evolutionary constraints and design principles of transcription networks beyond the yeast system. In addition, specific knowledge of transcriptional regulation in yeast can be transferred to higher eukaryotes including humans, since many biological processes are highly conserved. PUBLIC HEALTH RELEVANCE: Cellular transcription networks regulate essentially all biological processes, including development, cancer and aging. Mis-regulation of these processes leads to human diseases. A global understanding of the structure, function and evolution of the transcription networks in yeast will likely lead to general principles applicable to humans and have a significant impact on human health.