GATA-1, EKLF Synergistically Activate The Transcription Of HSA-MIR-144/451 Via Binding Its' Upstream Region

Human hematopoiesis is a very complex and multistep developmental process that starts from the level of pluripotent hematopoietic stem cells (HSCs) at bone marrow microenvironment (HSCs niche) and terminates with the production of erythrocytes. The main program involves self-renewal, directionally differentiation and functions maturity hematopoietic stem cells, and contains numerous complex regulated process. Erythropoiesis beginning at production of pluripotent hematopoietic stem cells is an important branching of hematopoiesis and gradually develops to erythroid precursors. Then, erythroid precursors are differentiated into erythropoietin (Epo)-responsive erythroid burst forming unit-erythroid (BFU-E) and colony forming unit-erythroid(CFU-E). The CFU-Es are finally differentiated into red blood cells (RBCs) via several differentiation processes. Erythropoiesis is regulated by many transcriptional factors, such as GATA-1, FOG-1 and EKLF which play great important role in different phase of erythropoisis. These transcriptional factors themselves are regulated by many small molecules, one of which is microRNA. MicroRNAs (miRNAs) are a class of small molecules family that plays great important regulated function to modulate target gene expression at post-transcription level. Universally, they are about 21-25nt in length and highly conserved among species. With number increasing and in-depth study of function, microRNA has been shown to be involved in all aspects of life and many diseases. Recently, several miRNAs have been characterized to be involved in hematopoiesis.MiR-144/451 cluster has now been recognized that is closely related to the erythroid differentiation. Some literatures have reported that erythroid specific transcription factor GATA-1 is able to bind to upstream of miR-144/451 cluster and then active RNA polymerase II-mediated transcription process.Our study firstly demonstrate that GATA-1, EKLF can bind to conserved motif of upstream of has-miR-144/451, and Preliminary research into its'regulated function on miR-144/451 cluster, which established experimental foundation for the study of erythroid transcription factor synergistic regulation to has-miR-144/451.