ATP-dependent and independent mechanisms of regulating chromatin states

摘要 遗传物质被分离成活跃转录的(常染色质)并受到遗传抑制 (异染色质)染色质状态对于维持细胞特性是必不可少的。这些染色质 依赖于三磷酸腺苷的染色质重塑的共同作用维持和重排状态 马达和特定的染色质结合蛋白。拟议的工作旨在研究核心 这些染色质调节器的机制，以实现更好地了解它们的活动是如何 在体内受到调节。利用各种生物物理方法，我们发现染色质 重塑ATPase利用染色质最小单位内的意外可塑性 核小体。塑料核小体表明染色质存在额外的调节作用。 我们还发现了HP1蛋白的相分离行为，这是HP1蛋白的核心成分 异染色质。这些结果表明，异染色质的一些抑制功能可能 源于染色质在相分离的小体中的物理隔离。在这里，我们将在这些基础上 新的发现提出了以下问题： 1.染色质重塑马达是如何将三磷酸腺苷的降解与核小体构象的变化联系起来的？ 2.不同类别的重建器在机制上有什么不同？ 3.相分离在异染色质调节中的作用是什么？

Abstract The segregation of genetic material into actively transcribed (euchromatin) and heritably repressed (heterochromatin) chromatin states is essential for the maintenance of cell identity. These chromatin states are maintained and rearranged by the combined action of ATP-dependent chromatin remodeling motors and specific chromatin binding proteins. The proposed work is aimed at studying the core mechanisms of these chromatin regulators to achieve a better understanding of how their activities are regulated in vivo. Using a variety of biophysical approaches we have found that chromatin remodeling ATPases take advantage of unexpected plasticity within the smallest unit of chromatin, a nucleosome. A plastic nucleosome suggests the presence of additional regulatory roles for chromatin. We have also uncovered phase-separation behavior in HP1 proteins, which are core components of heterochromatin. These results suggest that some of the repressive functions of heterochromatin may arise from physical sequestration of chromatin in phase-separated bodies. Here we will build on these new discoveries to ask the following questions: 1. How do chromatin remodeling motors couple ATP hydrolysis to changes in nucleosome conformation? 2. What are the differences in mechanism between remodelers from different classes? 3. What is the role of phase-separation in heterochromatin regulation?