| Autor: |
Landry, Josette-Renée, Kinston, Sarah, Knezevic, Kathy, de Bruijn, Marella F.T.R., Wilson, Nicola, Nottingham, Wade T., Peitz, Michael, Edenhofer, Frank, Pimanda, John E., Ottersbach, Katrin, Göttgens, Berthold |
| Zdroj: |
Blood; March 2008, Vol. 111 Issue: 6 p3005-3014, 10p |
| Abstrakt: |
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 Runx1and Runx3. Chromatin immunoprecipitation confirmed that both Runxgenes are direct targets of Scl in the fetal liver and that Runx1is 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 Runx1loci and was shown to transactivate the Runx1element. 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. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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