Roles of histone methylation reader proteins in cell fate

组蛋白甲基化阅读器蛋白在细胞命运中的作用

• 批准号: RGPIN-2019-06843
• 负责人: Saltzman, Arneet
• 金额: $ 2.7万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=739137
• 关键词: Roles; histone; methylation; reader; proteins

Most of the cells in the body share the same genome or DNA sequence, yet they are able to carry out many distinct functions. This cell specialization depends on different sets of genes being turned on or off in different types of cells. This process, termed gene regulation, is also affected by how the genome is physically packaged. The DNA of the genome is wrapped around core particles called histone proteins to form a polymer called chromatin. The histone proteins are not merely structural scaffolds, but can be modified in different ways to help control how genes are turned on and off. Although many parts of the machinery that controls histone modifications, or `chromatin factors' have been identified, many outstanding questions remain. For example, the genome is large and contains tens of thousands of genes. How do chromatin factors identify their target genes? How do they work together or against each other in gene regulation? What makes them work differently in different types of cells? These questions are fundamental for understanding how a single cell develops into a mature organism and how improper control of this process can lead to diseases. To study these questions, we use a tiny worm that has proven to be a valuable research tool. It has a smaller genome, a simple, well-defined body plan, and many of its chromatin factors work in similar ways to other animals, including humans. Our broad objective is to identify new chromatin factors and to find where they bind in the genome, how they interact with each other, and how gene expression is affected when they are mutated. This work and the new tools that we develop will be beneficial for understanding gene regulation and animal development. In addition, the knowledge gained in these studies can be harnessed for future innovations in stem cell-based technologies.

身体中的大多数细胞共享相同的基因组或DNA序列，但它们能够执行许多不同的功能。这种细胞特化取决于不同类型细胞中不同的基因组的开启或关闭。这个过程被称为基因调控，也受到基因组物理包装方式的影响。基因组的DNA被包裹在称为组蛋白的核心颗粒上，形成一种称为染色质的聚合物。组蛋白不仅仅是结构支架，还可以通过不同的方式进行修饰，以帮助控制基因的开启和关闭。尽管已经确定了控制组蛋白修饰或“染色质因子”的机制的许多部分，但仍存在许多悬而未决的问题。例如，基因组很大，包含数以万计的基因。染色质因子如何识别它们的靶基因？它们在基因调控中是如何协同工作或相互对抗的？是什么让它们在不同类型的细胞中发挥不同的作用？这些问题对于理解单个细胞如何发育成一个成熟的有机体以及对这一过程的不当控制如何导致疾病是至关重要的。为了研究这些问题，我们使用了一种微小的蠕虫，它被证明是一种有价值的研究工具。它有一个更小的基因组，一个简单的，明确的身体结构，它的许多染色质因子的工作方式与其他动物相似，包括人类。我们的主要目标是确定新的染色质因子，并发现它们在基因组中的结合位置，它们如何相互作用，以及当它们发生突变时基因表达如何受到影响。这项工作和我们开发的新工具将有助于理解基因调控和动物发育。此外，在这些研究中获得的知识可以用于干细胞技术的未来创新。