Runx transcription factors in the development and function of the definitive hematopoietic system.
The Runx family of transcription factors (Runx1, Runx2, and Runx3) are highly conserved and encode proteins involved in a variety of cell lineages, including blood and blood-related cell lineages, during developmental and adult stages of life. They perform activation and repressive functions in the regulation of gene expression. The requirement for Runx1 in the normal hematopoietic development and its dysregulation through chromosomal translocations and loss-of-function mutations as found in acute myeloid leukemias highlight the importance of this transcription factor in the healthy blood system. Whereas another review will focus on the role of Runx factors in leukemias, this review will provide an overview of the normal regulation and function of Runx factors in hematopoiesis and focus particularly on the biological effects of Runx1 in the generation of hematopoietic stem cells. We will present the current knowledge of the structure and regulatory features directing lineage-specific expression of Runx genes, the models of embryonic and adult hematopoietic development that provide information on their function, and some of the mechanisms by which they affect hematopoietic function.
Medical Research Council (MRC) Molecular Hematology Unit, MRC Weatherall Institute for Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; and.
Marella
0000-0002-4934-4125
M
de Bruijn
MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom.
Elaine
0000-0001-8256-5635
E
Dzierzak
D000208:Acute Disease; D000818:Animals; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism
D050676:Core Binding Factor Alpha 2 Subunit; D009363:Neoplasm Proteins; C493728:RUNX1 protein, human