Transcriptional regulation of granulocyte and monocyte development

Friedman, Alan D.

doi:10.1038/sj.onc.1205324

Cited by 286 publications

(246 citation statements)

References 241 publications

(153 reference statements)

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“…It has also been reported that the C/EBPalphamediated myoblast to adipocyte transition of C2C12 takes place in the absence of adipocyte differentiation medium (Fux et al, 2004). C/EBPbeta and C/EBPalpha are also key molecules for myeloid development (Friedman, 2002) or hepatocyte differentiation (Flodby et al, 1996). C/EBPalpha À/À mice lack neutrophils and eosinophils, but retain monocytes, lymphocytes, erythroid cells and immature myeloblasts .…”

Section: Discussionmentioning

confidence: 93%

FMIP controls the adipocyte lineage commitment of C2C12 cells by downmodulation of C/EBPalpha

et al. 2006

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Fms interacting protein (FMIP) is a substrate for Fms tyrosine kinase, and a nuclear/cytoplasm shuttling protein with a leucine zipper. As the phosphorylation of FMIP is observed in insulin-stimulated preadipocytes, we examined the role of FMIP in adipocyte differentiation, using the mesenchymal multipotent stem cells, C2C12 cells, that can differentiate into adipocytes, muscle cells and osteoblasts. Ectopic expression of FMIP in C2C12 impairs the adipocyte differentiation induced by treatment with insulin, dexamethasone and 3-isobutyl-1-methylxanthine. These cells exhibit muscle phenotype with multinuclear morphology. Furthermore, knockdown of endogenous FMIP expression by small interfering RNA improves adipocytic lineage commitment of C2C12 cells, while impairing muscle differentiation. Upon stimulation with insulin, CCAAT/enhancer binding protein (C/EBP)-beta, but not C/EBPalpha, is upregulated in cells expressing ectopic FMIP, whereas in FMIP knockdown cells, C/EBPalpha is constitutively expressed. Ectopic expression of C/EBPalpha counteracts the effects of FMIP, whereas C/EBPalpha knockdown partially mimics the effects of FMIP in this system. Northern blot analysis and reverse transcriptase-polymerase chain reaction study reveal that ectopic FMIP-expressing cells do not contain the polyadenylated C/EBPalpha mRNA, but contain the C/EBPalpha pre-mRNA, suggesting that FMIP plays a role in RNA processing and/or export. Indeed, a member of the THO complex that plays a role in mRNA export, THOC1, is co-precipitated with FMIP. The data we have acquired on FMIP suggest that it is a target for tyrosine kinase receptors that potentiate mRNA export.

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Section: Discussionmentioning

confidence: 93%

FMIP controls the adipocyte lineage commitment of C2C12 cells by downmodulation of C/EBPalpha

et al. 2006

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“…HIF-1a and leukemic cell differentiation L-P Song et al induction failed to impact protein levels of AML1 and PU.1 (Figure 6a), other two hematopoiesis-critical transcription factors (Friedman, 2002). Later, we stably introduced five pairs of shRNAs to specifically interfere C/EBPa expression (shR-C) in U937T clone cell line.…”

Section: Hif-1a Induction Triggers Differentiation With Growth Arrestmentioning

confidence: 98%

“…Role of C/EBPa in HIF-1a-mediated myeloid cell differentiation C/EBPa, a critical transcription factor for myeloid cell differentiation (Friedman, 2002;Mueller and Pabst, 2006), has been shown to be required to activate growth factor receptor genes M-CSFR, G-CSFR and GM-CSFR. On the other hand, the physical and functional interaction between HIF-1a and C/EBPa proteins was reported previously (Jiang et al, 2005).…”

Section: Hif-1a Induction Triggers Differentiation With Growth Arrestmentioning

confidence: 99%

“…A small group of transcription factors, such as CCAAT/enhancer-binding protein a (C/EBPa), Runx1 (originally named acute myeloid leukemia 1 (AML1)) and PU.1, play crucial roles in controlling normal hematopoiesis (Friedman, 2002). The structural and functional abnormalities of these factors also contribute to the pathogenesis of AML, in which the normal differentiation program is blocked (Peterson and Zhang, 2004;Rosenbauer et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Hypoxia-inducible factor-1α-induced differentiation of myeloid leukemic cells is its transcriptional activity independent

Wang

Zhang

et al. 2007

Oncogene

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Hypoxia or hypoxia mimetic has been shown to induce differentiation together with the accumulation of hypoxiainducible factor-1a (HIF-1a) protein of myeloid leukemic cells and normal hematopoietic progenitors. To provide direct evidence for the role of HIF-1a in acute myeloid leukemia (AML) cell differentiation and its mechanisms, we generated myeloid leukemic U937T transformants, in which HIF-1a was tightly induced by tetracycline withdrawal. The results showed that the conditional HIF-1a induction triggered granulocytic differentiation of these transformants, while the suppression of HIF-1a expression by specific short hairpin RNAs (shRNAs) effectively inhibited hypoxia-induced differentiation of U937 cells, as evidenced by morphology, maturation-related antigens as well as expressions of myeloid differentiation signatures and hematopoietic cells-specific cytokine receptors. The specific shRNAs-inhibited expression of HIF-1b, an essential partner for transcription activity of HIF-1, failed, while the inhibition of hematopoietic differentiation-critical CCAAT/enhancer-binding protein-a (C/EBPa) significantly eliminated HIF-1a-mediated myeloid leukemic cell differentiation. Collectively, this work provided several lines of direct evidence for the role of HIF-1a protein through its nontranscriptional activity in myeloid cell differentiation, in which C/EBPa elicits a role as an effector downstream to HIF-1a. These discoveries would shed new insights for understanding mechanisms underlying leukemogenesis and designing the new therapeutic strategy for differentiation induction of AML.

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“…The expression of ELA2 is tightly controlled by a number of hematopoietic-specific transcription factors (Friedman, 2002). In transient reporter gene studies, the CCAAT-enhancer binding protein (C/EBP), c-Myb and PU.1 together with the AML1 have been implicated in regulating the expression of ELA2 (Oelgeschlager et al, 1996;Nuchprayoon et al, 1997;Nuchprayoon et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

ELA2 is regulated by hematopoietic transcription factors, but not repressed by AML1-ETO

et al. 2005

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A 117 bp fragment of the human ELA2 promoter has been characterized that can act as a minimal promoter for the expression of neutrophil elastase. Chromatin immunoprecipitation and siRNAs revealed that expression of ELA2 is regulated by the acute myeloid human leukemia 1 protein (AML1), C/EBPa, PU.1 and c-Myb transcription factors. ELA2 has also been investigated as a possible target of the leukemic fusion protein AML1-ETO resulting from the t(8;21) chromosomal translocation. AML1-ETO, like AML1, binds the ELA2 promoter in the myeloid cell lines Kasumi-1 and U937, but unexpectedly fails to significantly alter expression of ELA2. Although AML1-ETO downregulates the expression of C/EBPa, changes in C/EBPa expression do not correlate with changes in the expression of ELA2. Our observations indicate that AML1-ETO may not be a constitutive repressor of gene expression in every case in which it can associate with DNA, either on its own or in conjunction with C/EBPa. Since neither ETO nor AML1-ETO are typically expressed in hematopoietic progenitors, we hypothesize that it is the interactions between AML1-ETO and regulatory cofactors in disease-state cells that alter gene expression programs during hematopoiesis. These protein-protein interactions may not require simultaneous DNA binding by AML1-ETO for the deleterious effects of the fusion protein to be realized.

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Transcriptional regulation of granulocyte and monocyte development

Cited by 286 publications

References 241 publications

FMIP controls the adipocyte lineage commitment of C2C12 cells by downmodulation of C/EBPalpha

FMIP controls the adipocyte lineage commitment of C2C12 cells by downmodulation of C/EBPalpha

Hypoxia-inducible factor-1α-induced differentiation of myeloid leukemic cells is its transcriptional activity independent

ELA2 is regulated by hematopoietic transcription factors, but not repressed by AML1-ETO

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