Graded regulation of gene expression by PU.1

PU.1对基因表达的分级调控

• 批准号: 386046-2010
• 负责人: DeKoter, Rodney
• 金额: $ 2.4万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=528726
• 关键词: Graded; regulation; gene; expression; PU.1

Blood cells are generated from immature precursor cells through a process called differentiation. Differentiation is controlled by external factors, such as cytokines, and by internal factors, such as regulated gene expression. A protein called PU.1 is located in the nucleus of immature blood cell precursors and is essential for controlling "decisions" to differentiate into either lymphocytes or macrophages. PU.1 is an example of a protein that regulates gene expression by turning genes on or off. High levels of PU.1 efficiently promote macrophage differentiation, whereas low levels of PU.1 promote lymphocyte differentiation. However, how this works at the molecular level is not understood. In this proposal, we will determine if high PU.1 levels are able to simultaneously turn on macrophage genes and shut off lymphocyte genes. If PU.1 has both of these activities it would explain why it is so efficient at programming immature blood cell precursors. This information will allow us to design strategies to generate desired blood cell types from precursor cells in the laboratory.

血细胞是由未成熟的前体细胞通过分化过程产生的。分化受外部因素（如细胞因子）和内部因素（如受调节的基因表达）的控制。一种名为PU.1的蛋白质位于未成熟血细胞前体的细胞核中，对控制分化为淋巴细胞或巨噬细胞的“决定”至关重要。PU.1是一种通过开启或关闭基因来调节基因表达的蛋白质。高水平的PU.1能有效促进巨噬细胞分化，而低水平的PU.1能促进淋巴细胞分化。然而，这在分子水平上是如何起作用的还不清楚。在这个提议中，我们将确定高PU.1水平是否能够同时开启巨噬细胞基因和关闭淋巴细胞基因。如果PU.1具有这两种活性，就可以解释为什么它在编程未成熟血细胞前体方面如此有效。这一信息将使我们能够设计策略，在实验室中从前体细胞中产生所需的血细胞类型。