Chromatin remodeling at cell cycle exit

项目概要/摘要 在发育过程中必须精确控制细胞增殖以产生正确形状的组织， 组成和大小。终末分化通常与退出细胞周期相关，并与细胞周期的变化相关。 一种永久的有丝分裂后状态的转变这是一个重要的发展过程， 从细胞周期中分离出来的蛋白质很可能代表了成年动物中最常见的细胞状态。我们的数据显示 特异性核小体重塑在正确启动和维持细胞周期退出中的关键作用。这是 这与我们发现的许多基因调控元件的可及性在细胞周期中也发生变化相一致 退出.我们提出的研究目标是了解细胞周期基因表达是如何关闭的 在发育过程中的正确位置和时间，以建立和维持稳定的有丝分裂后状态， 分化组织。为了实现这一目标，我们提出了三个目标：1。为了确定特定的基因表达 和调节元件可及性的变化，这是由于细胞周期的退出，以及它们是如何改变后， 强迫细胞周期再进入2.为了确定发育信号如何协调细胞周期退出， 分化事件和3.了解特异性核小体重塑物在促进细胞周期中的作用 退出.

Project Summary/Abstract Cell proliferation must be precisely controlled during development to produce tissues of the correct shape, composition and size. Terminal differentiation is often associated with exit from the cell cycle and coupled with a switch to a permanently postmitotic state. This is an important developmental process, as permanent exit from the cell cycle is likely to represent the most common cellular state in adult animals. Our data indicates a critical role for specific nucleosome remodelers in proper initiation and maintenance of cell cycle exit. This is consistent with our finding that accessibility at many gene regulatory elements also changes during cell cycle exit. The goal of our proposed research is to understand how cell cycle gene expression is shut down at the right places and times during development to establish and maintain a stable postmitotic state in differentiating tissues. To accomplish this, we propose three aims: 1. To define the specific gene expression and regulatory element accessibility changes that are due to cell cycle exit and how they are altered upon forced cell cycle re-entry 2. To determine how developmental signals coordinate cell cycle exit with differentiation events and 3. To understand the role of specific nucleosome remodelers in promoting cell cycle exit.