Investigation of a regulatory loop between the transcription factor TAL1 and the miR-17-92 Cluster in cell aging and leukemia

研究细胞衰老和白血病中转录因子 TAL1 和 miR-17-92 簇之间的调节环路

• 批准号: 393118049
• 负责人: Professor Dr. Jörn Lausen
• 金额: --
• 依托单位: Institut für Biomedizinische Genetik (IBMG)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/393118049?language=en
• 关键词: Investigation; regulatory; loop; between; transcription

Transcription factors and microRNAs are key regulators of hematopoietic gene expression. Often regulatory loops between transcription factors and microRNAs are established, in which a given transcription factor regulates a specific microRNA. In turn this microRNA regulates the expression of the transcription factor posttranscriptional. Alterations in gene expression of regulatory factors such as transcription factors and microRNAs by mutation or epigenetic deregulation are often involved in leukemia. The transcription factor TAL1 and the miR-17-92 cluster are important for normal hematopoiesis and alterations in these regulators are associated with leukemia. Furthermore, age related alteration in miR-17-92 expression has been shown in different cell systems. Our data show that TAL1 and the microRNAs of the miR-17-92 cluster might establish a regulatory loop. We found that TAL1 regulates the expression of miR-17-92 and that a microRNA of the miR-17-92 cluster inhibits TAL1 posttranscriptional. In this project we want to study the mutual regulation of TAL1 and miR-17-92 in normal hematopoiesis and in leukemia. Furthermore, we want to study age related alterations in the regulatory loop between TAL1 and miR-17-92 in T cells and hematopoietic stem cells. A focus of these examinations will be TAL1 mediated epigenetic alterations of miR-17-92 expression.

转录因子和 microRNA 是造血基因表达的关键调节因子。通常在转录因子和 microRNA 之间建立调节环，其中给定的转录因子调节特定的 microRNA。反过来，这种 microRNA 调节转录后转录因子的表达。突变或表观遗传失调导致转录因子和 microRNA 等调控因子基因表达的改变通常与白血病有关。转录因子 TAL1 和 miR-17-92 簇对于正常造血非常重要，这些调节因子的改变与白血病相关。此外，不同细胞系统中已显示出与年龄相关的 miR-17-92 表达变化。我们的数据表明 TAL1 和 miR-17-92 簇的 microRNA 可能建立一个调节环。我们发现 TAL1 调节 miR-17-92 的表达，并且 miR-17-92 簇的 microRNA 抑制 TAL1 转录后。在这个项目中，我们想要研究 TAL1 和 miR-17-92 在正常造血和白血病中的相互调节。此外，我们想要研究 T 细胞和造血干细胞中 TAL1 和 miR-17-92 之间的调节环路与年龄相关的变化。这些检查的重点是 TAL1 介导的 miR-17-92 表达的表观遗传改变。