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周期的转录调控网络。了解这些调控网络是非常重要的，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节器结合的位置，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，该提案的具体目标是：1)确定候选细胞周期转录调控因子的基因组结合部位；2)确定在人类细胞周期中表达振荡的人类基因集；3)构建控制人类细胞周期的转录调控网络模型，并测试其关键特征；以及4)识别原代成纤维细胞和成纤维细胞肿瘤细胞中细胞周期调控的差异。控制人类细胞周期的转录调控网络将对生物学家具有基本价值，因为它们将揭示调控细胞表型的途径，并可能提出诊断和抗击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.