Runx1, c‐Myb, and C/EBPα couple differentiation to proliferation or growth arrest during hematopoiesis

Abstract

Immature hematopoietic precursors proliferate as they differentiate, whereas terminal differentiation is associated with cell cycle arrest. Stem cell lineage commitment and subseqent maturation is regulated predominantly by transcription factors. Runx1 and c-Myb act in early stage hematopoietic cells to both stimulate proliferation and differentiation, whereas C/EBPalpha, and perhaps other C/EBP family members, block progression from G1 to S and induce terminal maturation. Coupling of differentiation to either proliferation or growth arrest by transcription factors is likely an important regulatory mechanism in multiple developmental systems.

Distinct MicroRNA Expression Profile and Targeted Biological Pathways in Functional Myeloid-derived Suppressor Cells Induced by Δ9-Tetrahydrocannabinol in Vivo

“…Extensive cross-talk between these transcription factors is further known to control complex pathways of monocytic and granulocytic differentiation (48). Runx1 stimulates proliferation and differentiation of myeloid progenitors (49). Multiple overexpressed and underexpressed miRNA in THC-MDSC had good binding sites on Runx1 mRNA 3Ј-UTR, which indicated a typically complex, probably finely tuned miRNA regulatory circuit.…”

The Histone Acetyltransferase TIP60 Interacts with c-Myb and Inactivates Its Transcriptional Activity in Human Leukemia

“…TIP60 also interacts with C/EBP ␣ as a coactivator (4). C/EBP ␣ is a transactivator involved in hematopoietic lineage decisions and in proliferation control and is required for the synergistic activation of myeloid genes and for myeloid cell maturation (34,35). The expression of both C/EBP ␣ and TIP60 increase during retinoic acid-induced differentiated U937 cells (4).…”

Physical and functional interaction of Runt-related protein 1 with hypoxia-inducible factor-1α

“…Hence, we investigated whether HIF-1a impinges on transcriptional activity of Runx1. HeLa cells were transfected with Runx1 and/or HIF-1a-expressing vectors together with core-binding factor-b (CBF-b, a partner of Runx1 for its basic activity (Friedman, 2002)), the human macrophage colonystimulating factor receptor (M-CSFR) promoter (-416 to þ 71)-driven luciferase (M-CSFR-Luc, which contains Runx1-binding sites ) and pSV40-renilla. Twenty-four hours later, cells were incubated in 95 or 2% air for additional 24 h. As mentioned above, HeLa cells expressed undetectable Runx1 and HIF-1a proteins in 95% air, regardless of HIF-1a transfection (Figure 5a, lanes 1 and 2), whereas 2% air induced HIF-1a protein accumulation (Figure 5a, lanes 5 and 7), especially in cells transfected with HIF-1a (Figure 5a, lanes 6 and 8).…”

“…As discussed (Suda et al, 2000), angiogenesis and hematopoiesis, which have common ancestors (hemangioblasts or hematogenic endothelial cells), are closely linked and interactive with each other. Hematopoietic process is closely regulated by a series of transcription factors such as Runt-related protein 1 (Runx1, also called as acute myeloid leukemia-1, AML-1), CCAAT/enhancer-binding proteins (C/EBPs), PU.1 and others (Werner et al, 1999;Friedman, 2002). More intriguingly, hematopoiesis-related Runx1 was also shown to play an important role in angiogenesis (Namba et al, 2000;Aikawa et al, 2006).…”