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

Journal article

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.

Authors: Landry, JR; Kinston, S; Knezevic, K; de Bruijn, M; Wilson, N

• Publication status: Published
• Journal: Blood
• Volume: 111
• Issue: 6
• Pages: 3005-3014
• Publication date: 2008-03-01
• DOI: 10.1182/blood-2007-07-098830
• EISSN: 1528-0020
• ISSN: 0006-4971
• Language: English
• Keywords: Animals; Molecular Sequence Data; Proto-Oncogene Proteins; Liver; GATA2 Transcription Factor; Core Binding Factor Alpha 2 Subunit; Basic Helix-Loop-Helix Transcription Factors; Humans; Cell Separation; Cell Line; Mice; Gene Expression Regulation, Developmental; Conserved Sequence; Sequence Alignment; DNA-Binding Proteins; Core Binding Factor Alpha 3 Subunit; Base Sequence; Mice, Knockout; Metalloproteins; Yolk Sac; LIM Domain Proteins; Protein Binding; Adaptor Proteins, Signal Transducing