Molecular characterization of the MIER2 and MIER3 transcriptional regulatory complexes

MIER2 和 MIER3 转录调控复合物的分子表征

• 批准号: RGPIN-2018-04383
• 负责人: Gillespie, Laura
• 金额: $ 2.33万
• 依托单位: Memorial University of Newfoundland
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=684346
• 关键词: Molecular; characterization; MIER2; MIER3; transcriptional

When a cell receives an external stimulus or signal, it produces a response by altering the expression of specific set of genes. Some genes are activated, some are shut off, and all of this must be precisely coordinated in order to produce the proper response, whether it be to grow, to migrate or produce a hormone. The question is: how does this occur? My approach to answer this question began with studying how cells respond to fibroblast growth factor (FGF). FGF is a natural signal in the body and interestingly, it stimulates adult cells to proliferate but stimulates cells of an embryo to stop growing and become a specialized tissue, like muscle. My study of the cell's response to FGF, led to the discovery of a novel regulatory gene, called mier1, and the protein produced by this gene, MIER1, can control the expression of other genes. It can shut off genes required for a cell to proliferate and it can affect genes required for proper development of the embryo. Over the years, we have learned a lot about how MIER1 works at the molecular level. It acts like a hub to recruit other proteins to specific sites in the genome to form a large regulatory complex that functions to control expression of sets of genes.*** When the human genome was sequenced and analyzed, two other genes closely related to mier1 were identified: mier2 and mier3. My lab is the main lab in the world studying the two proteins, MIER2 and MIER3, encoded by these genes. Our evidence so far indicates that MIER2 and MIER3 can also recruit other proteins and form a complex that functions to control genes required for a cell to respond to a signal. However, their mode of action is distinct from the MIER1 complex and from each other. *** The goal of the research in this proposal is to characterize the MIER2 and MIER3 complexes and determine how they work. By doing so, we will obtain fundamental information about how the expression of groups of genes is synchronized to produce a very specific and unique cellular response. Ultimately, this would enable us to learn how to control cell behaviour.

当细胞受到外部刺激或信号时，它会通过改变一组特定基因的表达来产生反应。有些基因被激活，有些基因被关闭，所有这些都必须精确协调，才能产生适当的反应，无论是生长、迁移还是产生一种激素。问题是：这种情况是如何发生的？我回答这个问题的方法始于研究细胞对成纤维细胞生长因子(成纤维细胞生长因子)的反应。成纤维细胞生长因子是体内的一种自然信号，有趣的是，它刺激成年细胞增殖，但刺激胚胎细胞停止生长，成为像肌肉一样的特殊组织。我对细胞对成纤维细胞生长因子的反应的研究，导致发现了一种新的调控基因，称为mier1，由该基因产生的蛋白质MIER1可以控制其他基因的表达。它可以关闭细胞增殖所需的基因，还可以影响胚胎正常发育所需的基因。多年来，我们对MIER1在分子水平上的工作原理了解了很多。它就像一个中枢，将其他蛋白质招募到基因组的特定位置，形成一个大型调控复合体，功能是控制一组基因的表达。*当对人类基因组进行测序和分析时，发现了另外两个与mier1密切相关的基因：mier2和mier3。我的实验室是世界上研究由这些基因编码的两种蛋白质MIER2和MIER3的主要实验室。到目前为止，我们的证据表明，MIER2和MIER3还可以招募其他蛋白质，形成一个复合体，功能是控制细胞对信号做出反应所需的基因。然而，它们的作用模式不同于MIER1复合体，也不同于彼此。*本提案中的研究目标是描述MIER2和MIER3复合体的特征，并确定它们的工作原理。通过这样做，我们将获得关于如何同步一组基因的表达以产生非常特定和独特的细胞反应的基本信息。最终，这将使我们能够学习如何控制细胞的行为。