The T-Cell Oncogene Tal2 Is a Target of PU.1 and Upregulated during Osteoclastogenesis
Autor: | Jörn Lausen, Stefanie Herkt, Stephan Kolodziej, Helge Hussong, Nadine Courtial, Christian Mücke |
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Jazyk: | angličtina |
Rok vydání: | 2013 |
Předmět: |
Cellular differentiation
Molecular Sequence Data lcsh:Medicine Osteoclasts Biology Cell Line Mice Species Specificity Proto-Oncogene Proteins Basic Helix-Loop-Helix Transcription Factors Animals Humans ddc:610 Amino Acid Sequence lcsh:Science Promoter Regions Genetic Transcription factor Conserved Sequence Regulation of gene expression Multidisciplinary Base Sequence Macrophage Colony-Stimulating Factor GATA2 lcsh:R RANK Ligand Promoter Genomics HNF1B Molecular biology Cell biology Neoplasm Proteins Up-Regulation Genetic Loci Trans-Activators lcsh:Q TAL2 TAL1 Research Article |
Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 9, p e76637 (2013) |
ISSN: | 1932-6203 |
Popis: | Transcription factors play a crucial role in regulating differentiation processes during human life and are important in disease. The basic helix-loop-helix transcription factors Tal1 and Lyl1 play a major role in the regulation of gene expression in the hematopoietic system and are involved in human leukemia. Tal2, which belongs to the same family of transcription factors as Tal1 and Lyl1, is also involved in human leukaemia. However, little is known regarding the expression and regulation of Tal2 in hematopoietic cells. Here we show that Tal2 is expressed in hematopoietic cells of the myeloid lineage. Interestingly, we found that usage of the Tal2 promoter is different in human and mouse cells. Two promoters, hP1 and hP2 drive Tal2 expression in human erythroleukemia K562 cells, however in mouse RAW cells only the mP1 promoter is used. Furthermore, we found that Tal2 expression is upregulated during oesteoclastogenesis. We show that Tal2 is a direct target gene of the myeloid transcription factor PU.1, which is a key transcription factor for osteoclast gene expression. Strikingly, PU.1 binding to the P1 promoter is conserved between mouse and human, but PU.1 binding to P2 was only detected in human K562 cells. Additionally, we provide evidence that Tal2 influences the expression of the osteoclastic differentiation gene TRACP. These findings provide novel insight into the expression control of Tal2 in hematopoietic cells and reveal a function of Tal2 as a regulator of gene expression during osteoclast differentiation. |
Databáze: | OpenAIRE |
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