Regulatory Mechanisms of CD4+ T Cell Differentiation

我们的ENCODE提案旨在从功能上表征基因调控过程中的变化， 小鼠CD 4 + T细胞的分化。我们已经完成了主要的主要目标， 在细胞分化期间改变活性的调节元件，以及鉴定调节元件 足以驱动细胞分化。我们还正在进行四年级的研究，以实现我们的目标， 测量上述调节元件对细胞周期中基因表达变化的影响， 分化最后，我们已经完成了几个人K562的跨ENCODE协调研究 和WTC-11细胞作为协调功能表征中心工作的一部分，现在 有助于对这些结果进行比较分析。我们有五个目标的这一要求， 扩展资金。首先，我们计划高效利用我们拥有的实验系统 迄今为止建立的用于表征涉及CD 4 T细胞的调节元件的基因靶点的方法， 分化第二，我们将继续我们的团队领导，比较不同的结果， ENCODE联盟的功能表征分析。第三，我们将扩大协调 功能表征的努力，包括对糖皮质激素的基因组反应的研究。 自2008年以来，ENCODE一直在研究糖皮质激素反应，包括功能性 在ENCODE结束时，对系统的特性研究将产生新的协同作用， 以前的数据生产工作。我们还认为，研究差异化监管的主题， 元素活动特别重要，因为所确定的元素和所使用的方法是 与稳态研究不同;因此，比较分析功能特性如何 技术在分析差异监管效应时的表现对于指导 未来的环境响应和扰动研究。第四，我们承诺提交所有数据 生成到ENCODE DCC。第五，我们还承诺分发所有试剂、方案和结果， 供社区使用的比较分析。延长供资的预期结果将 将大大提高ENCODE的实用性，为未来的基因组学研究提供信息，特别是 涉及高通量功能表征测定和/或涉及环境 应答这一结果符合ECP关于加强ENCODE研究的建议， 环境响应系统，并加强数据制作和功能之间的协调 特征中心。这些成果将对ENCODE的遗产产生特别影响， NHGRI广泛采取行动，增加对环境反应和基因组学研究的重视 作为2020年战略计划的一部分。

Our ENCODE proposal aims to functionally characterize changes in gene regulation during the differentiation of mouse CD4+ T cells. We have already accomplished major primary goals of identifying regulatory elements that change activity during cell differentiation, and identifying regulatory elements that are sufficient to drive cell differentiation. We also have ongoing Year 4 studies to achieve our Aim of measuring effects of above-described regulatory elements on changes in gene expression during cell differentiation. Finally, we have completed several cross-ENCODE coordinated studies of human K562 and WTC-11 cells as part of the coordinated functional characterization center effort, and are now contributing to the comparative analysis of those results. We have five objectives of this request for an extension of funding. First, we plan to make highly efficient use of the experimental systems we have established to date to characterize gene targets of regulatory elements involved in CD4 T cell differentiation. Second, we will continue our teams leadership in comparing results from different functional characterization assays across the ENCODE consortium. Third, we will expand coordinated functional characterization efforts to include study of the genomic response to glucocorticoids. Glucocorticoid responses have been studied by ENCODE since 2008, and including functional characterization studies of the system at the conclusion of ENCODE will create new synergies with those previous data production efforts. We also view the theme of studying differential regulatory element activity as particularly important because the elements identified and the methods used are distinct from steady-state studies; and thus comparative analyses of how functional characterization technologies perform when assaying differential regulatory effects will be invaluable for guiding the future environmental response and perturbation studies. Fourth, we commit to submitting all data generated to the ENCODE DCC. Fifth, we also commit to distributing all reagents, protocols and results from comparative analyses for community use. The expected outcome of this extension of funding will be to substantially enhance the utility of ENCODE to inform future genomics research, particularly that involving high-throughput functional characterization assays and/or that involving environmental responses. That outcome aligns with recommendations by the ECP to enhance ENCODE studies of environmental response systems and to enhance coordination between data production and functional characterization centers. Those outcomes will be particularly impactful in the legacy of ENCODE as the NHGRI moves broadly to increase emphasis on studies of environmental responses and genomic perturbations as part of the 2020 Strategic Plan.