Nucleation of Polycomb silencing at FLC

迪恩研究小组研究了参考植物拟南芥（Arabidopsis thaliana）开花时间的控制。几种开花途径会聚在一起调节一种称为FLC的基因，该基因表达的变化极大地促进了从世界各地收集的拟南芥类型开花时间的自然变化。冬季条件关闭了FLC基因的表达，解除了开花的制动，从而加速了开花过程。这种通过长时间暴露在冬季的寒冷中诱导植物开花的过程被称为“春化作用”。“对春化作用的遗传、分子和计算分析表明，它涉及一种细胞记忆机制，这种机制也发生在我们自己身体的发育过程中。在植物中，寒冷关闭FLC的表达，这种受抑制的状态由Polycomb蛋白维持，Polycomb蛋白将甲基化基团添加到与FLC DNA相关的蛋白质中。这些修饰从母体DNA链传递到子代DNA链，以在发育过程中保持基因的抑制状态，因为表观遗传调节和类似的机制在脊椎动物发育期间保持数千个基因关闭（沉默）。表观遗传学领域的一个关键问题是什么决定了一个特定的基因是否沉默。Dean实验室最近的工作在这个问题上取得了进展，通过表征FLC基因序列的变化，阻断了冷沉默。这使得能够识别与该特定区域结合的因子。然后，使用该因子的标记版本能够分离出一系列蛋白质，这些蛋白质在许多情况下是意想不到的，并表明可能参与沉默开关的蛋白质。该提案旨在跟进这些发现，以充分描述指定表观遗传沉默基因所需的多种因素。从这样的研究中了解可以提供对许多基因组的表观遗传调控重要的概念。

The Dean group studies the control of flowering time in the reference plant, thalecress (Arabidopsis thaliana). Several flowering pathways converge to regulate a gene called FLC and variation in expression of this gene contributes enormously to natural variation in flowering time of Arabidopsis types collected from around the world. Winter conditions switch off expression of the FLC gene, removing the brake to flowering, and thus accelerating the flowering process. This induction of a plant's flowering process by exposure to the prolonged cold of winter is termed "vernalization." Genetic, molecular and computational analysis of vernalization in thalecress has shown it involves a cellular memory mechanism, one that also occurs during development of our own bodies. In the plant, cold switches off expression of FLC and this repressed state is maintained by Polycomb proteins that add methylation groups to proteins associated with FLC DNA. These modifications are passed from the mother to the daughter DNA strand to maintain the repressed state of the gene through the development as epigenetic regulation and similar mechanisms keep many thousands of genes switched off (silenced) during vertebrate development. A key question in the epigenetic field is what determines whether a specific gene becomes silenced or not. Recent work in the Dean lab has made progress in this question through characterization of a change in the sequence of the FLC gene that blocks the silencing by cold. This then enabled the factor that binds to that specific region to be identified. Use of a tagged version of the factor then enabled isolation of a range of proteins that were in many cases unexpected and which suggested what might be involved in the silencing switch. This proposal aims to follow up these findings to fully describe the multiple factors required to specify a gene for epigenetic silencing. Understanding from a study such as this can provide concepts important to epigenetic regulation across many genomes.