Human Cell Cycle Transcriptional Regulatory Networks

描述（由申请人提供）：我们建议使用新开发的实验和计算技术来开始绘制控制人类细胞中细胞周期的转录调控网络。理解这些调控网络至关重要，因为许多生物过程和疾病都以某种方式与细胞周期控制有关。转录调控网络可以通过识别活细胞基因组中调控因子结合的位点，并将这些信息与基因表达数据相结合来绘制。为了实现这一目标，该计划的具体目标是：1）确定人类细胞中候选细胞周期转录调控因子的基因组结合位点; 2）鉴定在人类细胞中细胞周期期间表达振荡的人类基因组; 3）构建控制人类细胞周期的转录调控网络的模型并测试其关键特征;和4）鉴定原代成纤维细胞和成纤维细胞肿瘤细胞中细胞周期调节之间的差异。控制人类细胞周期的转录调控网络将对生物学家具有重要价值，因为它们将揭示细胞表型调控的途径，并可能提出诊断和对抗与细胞周期调控缺陷相关的疾病的新策略。

DESCRIPTION (provided by applicant): We propose to use newly developed experimental and computational technologies to begin mapping the transcriptional regulatory networks that control the cell cycle in human cells. It is fundamentally important to understand these regulatory networks, as many biological processes and diseases are connected in some manner to cell cycle control. Transcriptional regulatory networks can be mapped by identifying the sites bound by regulators throughout the genome of living cells, and by combining this information with gene expression data. To accomplish this, the specific aims of the proposal are: 1) Determine the genomic binding sites of candidate cell cycle transcriptional regulators in human cells; 2) Identify the set of human genes whose expression oscillates during the cell cycle in human cells; 3) Construct a model of the transcriptional regulatory network that controls the human cell cycle and test its key features; and 4) Identify differences between cell cycle regulation in primary fibroblasts and fibroblast tumor cells. The transcriptional regulatory networks that control the human cell cycle will be of fundamental value to biologists because they will reveal pathways by which cellular phenotypes are regulated and may suggest new strategies to diagnose and combat diseases associated with defects in cell cycle regulation.