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

• Applicant: Professor Dr. Jörn Lausen
• Subject Area: Hematology, Oncology ; Cell Biology
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 393118049

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.

• DFG Programme: Research Grants