Related Experiment Videos
DEC1 is a downstream target of TGF-beta with sequence-specific transcriptional repressor activities
Leigh Zawel1, Jian Yu, Christopher J Torrance
1The Howard Hughes Medical Institute and The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, 1650 Orleans Street, Baltimore, MD 21231, USA.
Abstract:
To identify genes that mediate transforming growth factor-beta (TGF-beta) signaling, a colorectal cancer cell line that was sensitive to the growth inhibitory effects of this cytokine was created. We then determined the global gene expression profiles of these cells, and those of HaCaT human keratinocytes, in the presence and absence of TGF-beta. Of the several genes identified in this screen, DEC1 was of particular note in light of the rapidity and consistency of its induction and its potential biochemical activities. We identified a consensus DNA-binding site for DEC1 and showed that DEC1 could repress the transcription of a reporter containing this binding site in its promoter. Finally, both alleles of the DEC1 locus in HaCaT cells were inactivated through targeted homologous recombination. This approach revealed that DEC1 induction was not required for the growth inhibition mediated by TGF-beta in this line. However, DEC1 may function in concert with other signaling components to mediate certain biologic effects of TGF-beta.
Insights
Researchers identified the gene DEC1 as rapidly induced by transforming growth factor-beta (TGF-beta). However, DEC1 is not essential for TGF-beta-mediated growth inhibition in colorectal cancer cells.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Transforming growth factor-beta (TGF-beta) is a crucial cytokine regulating cell growth and differentiation.
- Understanding the genes mediating TGF-beta signaling is vital for cancer research.
Purpose of the Study:
- To identify novel genes involved in TGF-beta signaling pathways.
- To investigate the role of the gene DEC1 in TGF-beta-mediated cellular responses.
Main Methods:
- Global gene expression profiling of colorectal cancer cells and HaCaT keratinocytes treated with TGF-beta.
- Identification and characterization of DEC1 DNA-binding sites.
- Gene knockout of DEC1 using targeted homologous recombination in HaCaT cells.
Main Results:
- DEC1 was rapidly and consistently induced by TGF-beta.
- DEC1 was found to repress transcription via a specific DNA-binding site.
- Inactivation of DEC1 did not abolish TGF-beta-induced growth inhibition in HaCaT cells.
Conclusions:
- DEC1 is a TGF-beta-responsive gene but is not essential for TGF-beta-mediated growth inhibition.
- DEC1 may collaborate with other signaling molecules to mediate specific TGF-beta biological effects.