Combinatorial action of RUNX1 and PU.1 in the regulation of hematopoiesis.
The hematopoietic stem cell (HSC) has the potential to differentiate into mature cells with distinct phenotypes and functions. As suggested in recent reports, this plasticity can expand to include nonhematopoietic lineages, and, indeed, the HSC may repopulate liver and muscle tissues, as well. Considering the flexibility in HSC differentiation, these processes are regulated by a relatively small number of factors, some of which are expressed in all lineages, whereas others are activated only in a specific cell type. Combined evidence from many studies suggests that alternative subsets of these factors work in a combinatorial manner to regulate specific promoters for the induction of a specific lineage. RUNX1 and PU.1 have a fundamental role in HSC differentiation in that multifactor complexes are assembled around these proteins leading to tissue-specific and synergistic gene activation. Here we describe the relationship of RUNX1 with PU.1 as a facet of the combinatorial relationships that determine hematopoietic lineage commitment.
Saunthararajah
Yogen
Y
Department of Medicine and Cancer Center, University of Illinois at Chicago, Chicago, IL 60612, USA. yogen@uic.edu
Boccuni
Piernicola
P
Nucifora
Giuseppina
G
D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000502:physiology; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000235:genetics; D008954:Models, Biological; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D014178:Translocation, Genetic; D000099232:Proto-Oncogene Protein Spi-1
D022763:CCAAT-Enhancer-Binding Protein-alpha; D050676:Core Binding Factor Alpha 2 Subunit; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1