Runx genes are direct targets of Scl/Tal1 in the yolk sac and fetal liver

Josette-Renee Landry, Sarah Kinston, Kathy Knezevic, Marella F. T. R. de Bruijn, Nicola Wilson, Wade T. Nottingham, Michael Peitz, Frank Edenhofer, John E. Pimanda, Katrin Ottersbach, Berthold Goettgens*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 SO 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.

Original languageEnglish
Pages (from-to)3005-3014
Number of pages10
JournalBlood
Volume111
Issue number6
DOIs
Publication statusPublished - 15 Mar 2008

Keywords

  • HEMATOPOIETIC STEM-CELLS
  • C-KIT EXPRESSION
  • ENDOTHELIAL-CELLS
  • TRANSCRIPTIONAL REGULATION
  • DEFINITIVE HEMATOPOIESIS
  • VASCULAR DEVELOPMENT
  • MAMMALIAN GENOMES
  • CRE RECOMBINASE
  • BLOOD FORMATION
  • AGM REGION

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