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Complexity in transcription control at the activation domain-mediator interface
Michael A Balamotis1, Mario A Pennella, Jennitte L Stevens
1Department of Microbiology, Immunology and Molecular Genetics, Molecular Biology Institute, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Science Signaling
|May 7, 2009
Summary
Med23 loss halts Egr1 transcription in stem cells but not fibroblasts, revealing cell-specific transcription factor roles in regulating gene expression via signal pathways.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Transcriptional regulation of Egr1 (early growth response factor 1) involves paused polymerase II.
- Mitogen-activated protein kinase (MAPK) pathway activation of ternary complex factor (TCF) ELK1 is crucial for Egr1 transcription.
- ELK1 interacts with the MED23 subunit of the Mediator complex.
Purpose of the Study:
- To investigate the role of MED23 in Egr1 transcription.
- To understand cell-type specific differences in Egr1 regulation between embryonic stem (ES) cells and fibroblasts.
- To elucidate the function of different TCF family members in Egr1 gene expression.
Main Methods:
- Med23 knockout (KO) in embryonic stem cells and fibroblasts.
- Chromatin immunoprecipitation (ChIP) assays.
- Live-cell imaging of fluorescently labeled proteins.
- Transcriptome analysis (RNA sequencing).
Main Results:
- Med23 KO nearly abolished Egr1 transcription in ES cells, leaving polymerase paused.
- Egr1 transcription was not eliminated by Med23 KO in fibroblasts.
- Three related TCFs bind to Egr1 regulatory regions, with differential responses to MED23 loss and varying expression levels in ES cells versus fibroblasts.
Conclusions:
- MED23 is essential for Egr1 transcription in ES cells, but not fibroblasts.
- Cell-type specific expression and function of TCFs contribute to differential Egr1 regulation.
- Alternative transcription factors mediate gene expression in response to signal transduction pathways in a cell-specific manner.
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