Regulation of RUNX1 transcriptional function by GATA-1.
Runt-related transcription factor 1 (RUNX1) and GATA-1 are both transcription factors known to play essential roles in hematopoiesis. Genetic alterations of each are associated with abnormal platelet development, as well as predisposition to leukemia. In addition, in vitro and animal studies indicate that both factors are involved in megakaryopoiesis. We and others have previously shown that RUNX1 and GATA-1 physically interact and cooperate in the activation of megakaryocytic promoters such as alpha IIb integrin and glycoprotein Ibalpha. Moreover, transcriptional cooperation of RUNX1 with GATA-1 is conserved back to Drosophila in which RUNX1 and GATA-1 homologs cooperate in crystal cell development. In this article, we will review the molecular and functional significance of the transcriptional cross talk between RUNX1 and GATA-1. In particular, we will elaborate on recent data which suggest that GATA-1 targets RUNX1 for modification, in particular phosphorylation by cyclin-dependent kinases. Furthermore, targeting of RUNX1 by GATA-1 for phosphorylation may convert RUNX1 from a repressor to an activator. This is a potential mechanism of transcriptional cooperation and may be an essential step in megakaryocytic differentiation.
Elagib
Kamaleldin E
KE
Department of Pathology, University of Virginia School of Medicine, PO Box 800904, Charlottesville, VA 22908, USA. ka8b@virginia.edu
Goldfarb
Adam N
AN
D000818:Animals; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D009154:Mutation; D010766:Phosphorylation; D014158:Transcription, Genetic / Q000502:physiology*
D050676:Core Binding Factor Alpha 2 Subunit; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; C493726:Runx1 protein, mouse