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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Base Sequence
-
Basic Helix-Loop-Helix Transcription Factors / chemistry
-
Basic Helix-Loop-Helix Transcription Factors / genetics*
-
Cell Line
-
Conserved Sequence
-
Genetic Loci / genetics
-
Genomics
-
Humans
-
Macrophage Colony-Stimulating Factor / pharmacology*
-
Mice
-
Molecular Sequence Data
-
Neoplasm Proteins / chemistry
-
Neoplasm Proteins / genetics*
-
Osteoclasts / cytology*
-
Osteoclasts / drug effects
-
Osteoclasts / metabolism*
-
Promoter Regions, Genetic / drug effects
-
Promoter Regions, Genetic / genetics
-
Proto-Oncogene Proteins / metabolism*
-
RANK Ligand / pharmacology*
-
Species Specificity
-
Trans-Activators / metabolism*
-
Up-Regulation* / drug effects
Substances
-
Basic Helix-Loop-Helix Transcription Factors
-
Neoplasm Proteins
-
Proto-Oncogene Proteins
-
RANK Ligand
-
TAL2 protein, human
-
Trans-Activators
-
proto-oncogene protein Spi-1
-
Macrophage Colony-Stimulating Factor
Grants and funding
This work was supported in part by the LOEWE initiative Onkogene Signaltransduktion Frankfurt, the LOEWE Center for Cell and Gene Therapy Frankfurt, Hessisches Ministerium für Wissenschaft und Kunst, III L 4-518/55.004 and III L 4-518/17004, the Deutsche Forschungsgemeinschaft (SPP-1463, LA 1389/5-1) and institutional funds of the Georg-Speyer-Haus. The Georg-Speyer-Haus is funded jointly by the German Federal Ministry of Health and the Ministry of Higher Education, Research and the Arts of the state of Hessen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.