Constitutive Expression of PU.1 in Fetal Hematopoietic Progenitors Blocks T Cell Development at the Pro-T Cell Stage

Anderson, Michele K.; Weiss, Angela; Hernández-Hoyos, Gabriela; Dionne, Christopher J.; Rothenberg, Ellen V.

doi:10.1016/s1074-7613(02)00277-7

Cited by 155 publications

(165 citation statements)

References 32 publications

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“…In the adult, ets-1 is expressed in the granulation tissue during wound healing, but also in endothelial cells of solid tumors (Wernert et al, 1992;Vandenbunder et al, 1994) and in the tissue stroma in reaction to tumors Calmels et al, 1995). ets-1 is also expressed in haematopoietic cells (Kola et al, 1993), during the lymphoid differentiation (Anderson et al, 1999), and seems to play an important role in T-cell survival (Bories et al, 1995) and the establishment of NK cells (Barton et al, 1998). In all these reports, the full-length Ets-1 molecule was commonly considered to be the active form and the role of the ets-1-dVII splice variant has understandably not been addressed.…”

Section: Discussionmentioning

confidence: 99%

Characterization and functional analysis of the p42Ets-1 variant of the mouse Ets-1 transcription factor

et al. 2003

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We have identified the mouse exon VII splice variant of the Ets-1 transcription factor. The variant is expressed in all cell lines which express ets-1, at lower levels, it is also expressed in the mouse embryo in vivo. The corresponding protein, p42Ets-1, is a transcription factor as it is able to bind to specific DNA sequences and to transactivate a bona fide ETS reporter vector. A comparison of optimal DNA-binding sites shows that p42Ets-1 binds to more various DNA sequences than p51Ets-1; p42Ets-1 recognizes the same optimal consensus sequence as p51Ets-1, but also many variations of it, mainly at base À1, which is located just prior to the GGAA/T core sequence. The binding differences were quantified by surface plasmon resonance analyses and the protein region responsible for the differences in DNA sequence recognition located in the Val 280 -Glu 302 fragment, which is encoded by exon VII. The specific DNA-binding properties of each isoform translates into clear differences in activity, p42Ets-1 transactivates the natural VE-cadherin gene promoter through both ETS-binding site (EBS)2 and EBS4 whereas p51Ets-1 is mainly active on EBS4. Altogether, our data suggest that p42Ets-1 acts as a distinct transcription factor from p51Ets-1. Oncogene (2003) 22, 9156-9164.

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Section: Discussionmentioning

confidence: 99%

Characterization and functional analysis of the p42Ets-1 variant of the mouse Ets-1 transcription factor

et al. 2003

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“…The level of PU.1 expression is critical for specifying cell fate, and, if perturbed, even modest decreases in PU.1 can lead to leukemias and lymphomas (Moreau-Gachelin et al 1988;DeKoter and Singh 2000;Anderson et al 2002;Rothenberg and Anderson 2002;Dahl et al 2003;Cook et al 2004;Rosenbauer et al 2004Rosenbauer et al , 2006Huang et al 2008). Previous reports demonstrated regulation of the PU.1 gene through the proximal promoter (Chen et al 1995) and an upstream regulatory element (URE) located −14 kb and −17 kb upstream of the transcription start sites (TSS) in mice and humans, respectively (Li et al 2001;Rosenbauer et al 2004;Okuno et al 2005).…”

mentioning

confidence: 99%

PU.1 expression is modulated by the balance of functional sense and antisense RNAs regulated by a shared cis-regulatory element

Ebralidze¹,

Guibal²,

Steidl³

et al. 2008

Genes Dev.

164

147

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The transcription factor PU.1 is an important regulator of hematopoiesis; precise expression levels are critical for normal hematopoietic development and suppression of leukemia. We show here that noncoding antisense RNAs are important modulators of proper dosages of PU.1. Antisense and sense RNAs are regulated by shared evolutionarily conserved cis-regulatory elements, and we can show that antisense RNAs inhibit PU.1 expression by modulating mRNA translation. We propose that such antisense RNAs will likely be important in the regulation of many genes and may be the reason for the large number of overlapping complementary transcripts with so far unknown function.[Keywords: Noncoding antisense RNA; upstream and intronic regulatory elements; coordinated expression of the target and regulator; translation stalling] Supplemental material is available at http://www.genesdev.org.

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“…Finally, the role of circulating proinflammatory cells in the promotion of FGF-2-mediated angiogenesis should also be considered. Indeed, several Ets factors are expressed in cells of the immune system (Anderson et al, 1999). Since members of the Ets family present homologies in their DNAbinding domain, we cannot exclude that the competition of Ets1-DB with Ets factors responsible for the activation of these proinflammatory cells recruited by FGF-2 contributes to the strong reduction in the FGF-2 angiogenic phenotypes recorded in the ear model.…”

Section: Involvement Of Ets Transcription Factors In Fgf-2-and Tumor-mentioning

confidence: 96%

Expression of an Ets-1 dominant-negative mutant perturbs normal and tumor angiogenesis in a mouse ear model

et al. 2003

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We and others have shown that members of the Ets family of transcription factors are involved in morphogenic properties of endothelial cells in vitro. To investigate the role of these factors in the transcriptional regulation of angiogenesis in vivo, we set up a nontraumatic model that allows daily macroscopic examination of both growth factor-and tumor-induced angiogenesis in mouse ears. In the same animal, we were thus able to record variations in the patterns of neovessels induced and cell populations recruited by the angiogenic factors FGF-2 and VEGF. In this model, inhibition of FGF-2-induced angiogenesis by the pharmacological compound TNP-470 was readily observed, demonstrating that the mouse ear model is also useful in the evaluation of antiangiogenic strategies. Our functional analysis of Ets transcription factors activity utilized a competitor protein, Ets1-DB, a dominant negative Ets1 mutant lacking the transactivation domain. Retrovirus-mediated expression of Ets1-DB inhibited FGF-2-induced angiogenesis, while the expression of Ets1-DB in cancerous and stromal cells disturbed tumorinduced angiogenesis. These results illustrate the value of the ear model and highlight the role of Ets family members in the transcriptional regulation of tumor angiogenesis.

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Constitutive Expression of PU.1 in Fetal Hematopoietic Progenitors Blocks T Cell Development at the Pro-T Cell Stage

Cited by 155 publications

References 32 publications

Characterization and functional analysis of the p42Ets-1 variant of the mouse Ets-1 transcription factor

Characterization and functional analysis of the p42Ets-1 variant of the mouse Ets-1 transcription factor

PU.1 expression is modulated by the balance of functional sense and antisense RNAs regulated by a shared cis-regulatory element

Expression of an Ets-1 dominant-negative mutant perturbs normal and tumor angiogenesis in a mouse ear model

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