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- Josette-Renée Landry
- Department of Haematology, Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom;
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- Sarah Kinston
- Department of Haematology, Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom;
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- Kathy Knezevic
- Department of Haematology, Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom;
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- Marella F.T.R. de Bruijn
- Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom; and
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- Nicola Wilson
- Department of Haematology, Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom;
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- Wade T. Nottingham
- Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom; and
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- Michael Peitz
- Stem Cell Engineering Group, Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn and Hertie Foundation, Bonn, Germany
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- Frank Edenhofer
- Stem Cell Engineering Group, Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn and Hertie Foundation, Bonn, Germany
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- John E. Pimanda
- Department of Haematology, Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom;
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- Katrin Ottersbach
- Department of Haematology, Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom;
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- Berthold Göttgens
- Department of Haematology, Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom;
書誌事項
- 公開日
- 2008-03-15
- DOI
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- 10.1182/blood-2007-07-098830
- 公開者
- American Society of Hematology
この論文をさがす
説明
<jats:title>Abstract</jats:title><jats:p>Transcription factors such as Scl/Tal1, Lmo2, and Runx1 are essential for the development of hematopoietic stem cells (HSCs). However, the precise mechanisms by which these factors interact to form transcriptional networks, as well as the identity of the genes downstream of these regulatory cascades, remain largely unknown. To this end, we generated an Scl−/− yolk sac cell line to identify candidate Scl target genes by global expression profiling after reintroduction of a TAT-Scl fusion protein. Bioinformatics analysis resulted in the identification of 9 candidate Scl target transcription factor genes, including Runx1 and Runx3. Chromatin immunoprecipitation confirmed that both Runx genes are direct targets of Scl in the fetal liver and that Runx1 is also occupied by Scl in the yolk sac. Furthermore, binding of an Scl-Lmo2-Gata2 complex was demonstrated to occur on the regions flanking the conserved E-boxes of the Runx1 loci and was shown to transactivate the Runx1 element. Together, our data provide a key component of the transcriptional network of early hematopoiesis by identifying downstream targets of Scl that can explain key aspects of the early Scl−/− phenotype.</jats:p>
収録刊行物
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- Blood
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Blood 111 (6), 3005-3014, 2008-03-15
American Society of Hematology
