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E-box sequence and context-dependent TAL1/SCL modulation of basic helix-loop-helix protein-mediated transcriptional
A L Nielsen1, P L Norby, F S Pedersen
1Department of Molecular Biology, Aarhus University, C. F. Mollers Allé 130, DK-8000 Aarhus C, Denmark. poul@biobase.dk
The Journal of Biological Chemistry
|December 6, 1996
Summary
The TAL1/SCL oncoprotein forms unique heterodimers with the ALF1 transcription factor, altering DNA binding specificity and resisting Id1 inhibition. This suggests TAL1
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- TAL1/SCL is a basic helix-loop-helix (bHLH) oncoprotein implicated in T-cell acute lymphoblastic leukemia (T-ALL).
- TAL1 is expressed in hematolymphoid cells but not in T- and B-lineage cells.
- The TAL1 gene is activated by chromosomal rearrangements in T-ALL.
Purpose of the Study:
- To investigate the dimerization partners of the TAL1/SCL oncoprotein.
- To characterize the DNA binding properties of TAL1/ALF1 heterodimers.
- To explore the role of Id1 in regulating TAL1/ALF1 transcriptional activity.
Main Methods:
- Co-immunoprecipitation to assess heterodimer formation.
- Electrophoretic mobility shift assays (EMSAs) to determine DNA binding specificity.
- Reporter gene assays to measure transcriptional activity in NIH3T3 cells.
Main Results:
- TAL1/SCL forms heterodimers with the ubiquitously expressed bHLH transcription factor ALF1.
- TAL1/ALF1 heterodimers exhibit distinct DNA binding specificity, preferring the Egre motif.
- Transcriptional activity of TAL1/ALF1 heterodimers is resistant to Id1 overexpression, unlike ALF1 homodimers.
Conclusions:
- ALF1 serves as a dimerization partner for TAL1/SCL, creating a complex with unique DNA binding properties.
- TAL1's leukemogenic potential may involve activating target genes via heterodimers with ubiquitous bHLH factors like ALF1.
- TAL1 might function by neutralizing Id-mediated inactivation of transcriptional activity.