Targets of the Tal1 transcription factor in erythrocytes: E2 ubiquitin conjugase regulation by Tal1.
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.
Lausen
Jörn
J
Georg-Speyer-Haus, Institute for Biomedical Research, D-60596 Frankfurt (Main), Germany. lausen@em.uni-frankfurt.de
Pless
Ole
O
Leonard
Fransisca
F
Kuvardina
Olga N
ON
Koch
Benjamin
B
Leutz
Achim
A
D018952:Antigens, CD34; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D004912:Erythrocytes / Q000378:metabolism*; D015672:Erythroid Precursor Cells / Q000378:metabolism*; D004920:Erythropoiesis / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D020014:K562 Cells; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000096:biosynthesis* / Q000235:genetics; D054875:Ubiquitination / Q000502:physiology
D018952:Antigens, CD34; D051792:Basic Helix-Loop-Helix Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes; C067143:TAL1 protein, human; C086376:UBE2H protein, human