Mechanisms of inheritance of histone-based information through DNA replication.

通过 DNA 复制继承组蛋白信息的机制。

• 批准号: RGPIN-2019-05040
• 负责人: Francis, Nicole
• 金额: $ 3.06万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744377
• 关键词: Mechanisms; inheritance; histone; based; information

Epigenetic inheritance is the study of inherited information, which affects how cells use their genetic material (or express genes), rather than the genes themselves. Our genetic material, DNA, is packaged with proteins into a structure called chromatin. Chromatin consists of repeating units of histones, proteins that organize the long threads of DNA into fibers. The structure of chromatin fibers is not identical at all genes; different structures are used to indicate which genes should be on or off genes will be active or silenced. These differences in chromatin at different genes are thought to be inherited when cells divide; this inheritance helps the two new cells remember which genes to express. However, the molecular process by which cell divide disrupts chromatin structure. Cells are likely to have strategies to preserve the information in chromatin structures cell division. Our goal is to discover these strategies. When cells copy their DNA, the histone proteins are dislodged. They are then put back once the DNA is copied. However, we do not know if they are put back at exactly the same place or somewhere nearby. This is important because histones are not the same at genes that are active versus silenced. Thus, each gene may need to keep its "own" histones to ensure that the correct expression state is copied. Our experiments are designed to test how well genes keep their own histones, and the strategies that are used to put histones back near where they started. When the genetic material is duplicated, some of the histones are transferred to one copy, and some to the other. The gaps left between the histones are filled by new histones. However, these new histones are generic and do not have information about gene expression patterns. Thus, there need to be mechanisms to make the new histones the same as the old ones at each gene. The two new copies of the genome, referred to as "sisters", are held together by a special protein complex called cohesin. Our project aims to test if the two new copies of the genome exchange information to ensure that the new histones on both copies are converted to the old state. The processes we are studying are essential for cells to maintain their identity, and may be disrupted in diseases like cancer that involve aberrant cell replication.

表观遗传是对遗传信息的研究，它影响细胞如何使用它们的遗传物质（或表达基因），而不是基因本身。我们的遗传物质，DNA，被蛋白质包装成一种叫做染色质的结构。染色质由组蛋白的重复单位组成，组蛋白是将DNA的长线组织成纤维的蛋白质。并非所有基因的染色质纤维结构都是相同的；不同的结构用来指示哪些基因应该开启或关闭，哪些基因将被激活或沉默。这些不同基因上的染色质差异被认为是在细胞分裂时遗传的；这种遗传有助于两个新细胞记住要表达的基因。然而，细胞分裂的分子过程破坏了染色质结构。细胞可能有策略来保存染色质结构中的信息，细胞分裂。我们的目标是发现这些策略。当细胞复制它们的DNA时，组蛋白被移除。一旦DNA被复制，它们就会被放回原处。然而，我们不知道它们是否被放回了完全相同的地方或附近的某个地方。这一点很重要，因为组蛋白在活性基因和沉默基因上是不一样的。因此，每个基因可能需要保持其“自己的”组蛋白，以确保正确的表达状态被复制。我们的实验旨在测试基因如何很好地保持它们自己的组蛋白，以及用来将组蛋白放回到它们开始的地方的策略。当遗传物质被复制时，一些组蛋白被转移到一个拷贝上，另一些转移到另一个拷贝上。组蛋白之间留下的空隙被新的组蛋白填充。然而，这些新的组蛋白是通用的，没有基因表达模式的信息。因此，需要有一种机制使每个基因上的新组蛋白与旧组蛋白相同。这两个新的基因组拷贝，被称为“姐妹”，由一种叫做内聚蛋白的特殊蛋白质复合物连接在一起。我们的项目旨在测试基因组的两个新拷贝是否交换信息，以确保两个拷贝上的新组蛋白转化为旧状态。我们正在研究的过程对于细胞保持其特性至关重要，并且可能在涉及异常细胞复制的癌症等疾病中被破坏。