Analyses of transcription factors related to megakaryocyte differentiation and maturation.

点击翻译按钮获取中文摘要

We have previously determined the cis-element that is responsible for the megakaryocyte specific expression of the PF4 gene and the proteins that bind to this element. In this study, we investigated the function of USFs and AML-1 which were involved in these proteins. We found that these transcription factors stimulated the expression of the PF4 gene. We further studied the biological function of AML-1. Although we could detect ETS-1 protein in the transcriptional complex including AML-1, we could not find CBFβ which up-regulated the transcriptional activity of AML-1 in the complex. We next investigated the function of AML-1 for the megakaryocyte differentiation. The knock down experiments of AML-1 by using RNAi revealed that AML-1 promoted the megakaryocyte differentiation and maturation at the early stage of megakaryopoiesis. However, AML-1 repressed the differentiation at the late stage of megakaryopoiesis.We also investigated the relationship between AML-1 mutations and familial platelet disorder (FPD). The transcriptional activities of AML-1 mutants on the PF4 gene expression were studied. We found that a certain AML-1 mutants not only diminished their own transcriptional activities but also inhibited the transcription by the wild type AML-1. Further analyses revealed that these mutants inhibited the transport of ETS-1 to the nucleus. These results provide us important information for the future approaches to the FPD research.