Targets of the Tal1 Transcription Factor in Erythrocytes

• Published in: The Journal of biological chemistry Vol. 285; no. 8; pp. 5338 - 5346
• Main Authors: Lausen, Jörn, Pless, Ole, Leonard, Fransisca, Kuvardina, Olga N., Koch, Benjamin, Leutz, Achim
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 19.02.2010; American Society for Biochemistry and Molecular Biology
• Subjects: Blood Erythropoeisis; Chromatin/Immunoprecipitation/ChIP; Development Differentiation/Hematopoietic; Diseases/Cancer/Leukemia; Gene/Transcription; Proteases/Ubiquitination; Transcription; Transcription; Blood Erythropoeisis; Diseases/Cancer/Leukemia; Proteases/Ubiquitination; Chromatin/Immunoprecipitation/ChIP; Gene/Transcription; Development Differentiation/Hematopoietic
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109.030296

The Tal1 transcription factor is essential for the development of the hematopoietic system and plays a role during definitive erythropoiesis in the adult. Despite the importance of Tal1 in erythropoiesis, only a small number of erythroid differentiation target genes are known. A chromatin precipitation and cloning approach was established to uncover novel Tal1 target genes in erythropoiesis. The BirA tag/BirA ligase biotinylation system in combination with streptavidin chromatin precipitation (Strep-CP) was used to co-precipitate genomic DNA bound to Tal1. Tal1 was found to bind in the vicinity of 31 genes including the E2-ubiquitin conjugase UBE2H gene. Binding of Tal1 to UBE2H was confirmed by chromatin immunoprecipitation. UBE2H expression is increased during erythroid differentiation of hCD34+ cells. Tal1 expression activated UBE2H expression, whereas Tal1 knock-down reduced UBE2H expression and ubiquitin transfer activity. This study identifies parts of the ubiquitinylation machinery as a cellular target downstream of the transcription factor Tal1 and provides novel insights into Tal1-regulated erythropoiesis.