MiR144/451 Expression Is Repressed by RUNX1 During Megakaryopoiesis and Disturbed by RUNX1/ETO.

ABSTRACT: A network of lineage-specific transcription factors and microRNAs tightly regulates differentiation of hematopoietic stem cells along the distinct lineages. Deregulation of this regulatory network contributes to impaired lineage fidelity and leukemogenesis. We found that the hematopoietic master regulator RUNX1 controls the expression of certain microRNAs, of importance during erythroid/megakaryocytic differentiation. In particular, we show that the erythorid miR144/451 cluster is epigenetically repressed by RUNX1 during megakaryopoiesis. Furthermore, the leukemogenic RUNX1/ETO fusion protein transcriptionally represses the miR144/451 pre-microRNA. Thus RUNX1/ETO contributes to increased expression of miR451 target genes and interferes with normal gene expression during differentiation. Fu

SUBMITTER: Kohrs N 

PROVIDER: S-EPMC4798443 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature