Nucleation of Polycomb silencing at FLC

FLC 下 Polycomb 沉默的成核

• 批准号: BB/P006590/1
• 负责人: Caroline Dean
• 金额: $ 90.16万
• 依托单位: John Innes Centre
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FP006590%2F1
• 关键词: Nucleation; Polycomb; silencing; FLC

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.

Dean小组研究了对照植物拟南芥（Arabidopsis thaliana）开花时间的控制。几种开花途径聚集在一起调节一个名为FLC的基因，该基因的表达变化对从世界各地收集的拟南芥类型开花时间的自然变化起着巨大的作用。冬季条件关闭了FLC基因的表达，消除了开花的刹车，从而加速了开花过程。这种通过暴露在冬季的长时间寒冷中来诱导植物开花的过程被称为“春化”。基因、分子和计算分析表明，丘脑休眠中的春化与细胞记忆机制有关，这一机制也发生在我们自己身体的发育过程中。在植物中，低温关闭FLC的表达，这种抑制状态由Polycomb蛋白维持，Polycomb蛋白向FLC DNA相关蛋白添加甲基化基团。这些修饰从母亲传递到女儿的DNA链，在整个发育过程中保持基因的抑制状态，因为表观遗传调控和类似的机制在脊椎动物发育过程中保持数千个基因的关闭（沉默）。表观遗传学领域的一个关键问题是，是什么决定了特定基因是否沉默。迪恩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，阻止了寒冷的沉默。这样就可以识别与特定区域结合的因子。然后，使用该因子的标记版本可以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，这表明沉默开关可能涉及什么。本研究旨在跟进这些发现，以充分描述指定表观遗传沉默基因所需的多种因素。从这样的研究中得到的理解可以为许多基因组的表观遗传调控提供重要的概念。

项目成果

Distinct accessory roles of Arabidopsis VEL proteins in Polycomb silencing.

• DOI: 10.1101/gad.350814.123
• 发表时间: 2023-09-01
• 期刊: Genes & development
• 影响因子: 10.5
• 作者: Franco-Echevarría E;Nielsen M;Schulten A;Cheema J;Morgan TE;Bienz M;Dean C
• 通讯作者: Dean C

Disruption of an RNA-binding hinge region abolishes LHP1-mediated epigenetic repression.

• DOI: 10.1101/gad.305227.117
• 发表时间: 2017-11-01
• 期刊: Genes & development
• 影响因子: 10.5
• 作者: Berry S;Rosa S;Howard M;Bühler M;Dean C
• 通讯作者: Dean C

Plant vernalization proteins contain unusual PHD superdomains without histone H3 binding activity.

• DOI: 10.1016/j.jbc.2022.102540
• 发表时间: 2022-11
• 期刊: The Journal of biological chemistry
• 作者: Franco-Echevarría E;Rutherford TJ;Fiedler M;Dean C;Bienz M
• 通讯作者: Bienz M

Head-to-tail polymerization by VEL proteins underpins cold-induced Polycomb silencing in flowering control.

• DOI: 10.1016/j.celrep.2022.111607
• 发表时间: 2022-11-08
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Fiedler M;Franco-Echevarría E;Schulten A;Nielsen M;Rutherford TJ;Yeates A;Ahsan B;Dean C;Bienz M
• 通讯作者: Bienz M

Cell-Size-Dependent Transcription of FLC and Its Antisense Long Non-coding RNA COOLAIR Explain Cell-to-Cell Expression Variation.

• DOI: 10.1016/j.cels.2017.05.010
• 发表时间: 2017-06-28
• 期刊: Cell systems
• 影响因子: 9.3
• 作者: Ietswaart R;Rosa S;Wu Z;Dean C;Howard M
• 通讯作者: Howard M