Abstract
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.
Highlights
The closely related basic helix-loop-helix transcription factors Tal1 (SCL1), Tal2 and Lyl1 are important regulators of normal development and differentiation
Our data show that Tal2 is expressed in the human erythroleukaemia cell line K562 and in the mouse monocyte/macrophage cell line RAW
Tal2 mRNA is upregulated upon receptor activator of NF-kB ligand (RANKL) induced osteoclast differentiation of mouse bone marrow derived monocytes/macrophages (BMM) cells and human U937 cells suggesting a role of Tal2 in this process
Summary
The closely related basic helix-loop-helix transcription factors Tal (SCL1), Tal and Lyl are important regulators of normal development and differentiation. Unlike Tal, the closely related Lyl protein is not needed for early hematopoietic development [2,3] and may have overlapping and independent functions with Tal in gene regulation [4]. The Tal protein is smaller than Tal and Lyl, because it lacks N-terminal transactivation or repression domains. Despite these differences, Tal, Lyl and Tal are associated with T-cell acute lymphoblastic leukaemia (T-ALL) [5]. Tal expression was connected to human epithelial ovarian cancer [15] This raises the question if Tal is causally connected to other cancer types than T-cell leukaemia
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