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Lymphoid enhancer binding factor 1 regulates transcription through gene looping.
Kangsun Yun1, Jae-Seon So, Arijita Jash
1Department of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
Journal of Immunology (Baltimore, Md. : 1950)
|September 29, 2009
Summary
Lymphoid enhancer binding factor 1 (Lef1) mediates gene looping between 5' and 3' DNA regions, enhancing transcription of target genes like COX2 and MMP13. This process involves Lef1 interacting with transcription factors upon IL-1beta stimulation.
Area of Science:
- Molecular Biology
- Gene Regulation
- Epigenetics
Background:
- Efficient gene transcription relies on physical and functional interactions between transcription machinery and DNA.
- Lymphoid enhancer binding factor 1 (Lef1) is known to regulate target genes COX2 and MMP13 in chondrocytes via 3' region binding.
Purpose of the Study:
- To investigate the mechanism by which 3'-region bound Lef1 regulates target gene expression.
- To elucidate the role of Lef1 in mediating gene looping and its impact on inducible gene transcription.
Main Methods:
- Chromosome conformation capture (3C) assay to analyze gene looping.
- Gene knockdown and overexpression studies of Lef1, RelA, and c-Jun.
- Analysis of physical interactions between Lef1 and transcription factors.
Main Results:
- IL-1beta stimulation induces gene looping in COX2 and MMP13 loci, bringing 5' and 3' regions together.
- Lef1 is crucial for gene looping; its knockdown reduces looping, while overexpression enhances it.
- Lef1 physically interacts with beta-catenin, AP-1, and NF-kappaB, with increased interactions upon stimulation, leading to synergistic gene upregulation.
Conclusions:
- Lef1 acts as a novel mediator of gene looping between 5' and 3' genomic regions.
- Gene looping facilitated by Lef1 may define transcription units in inducible mammalian gene expression.
- This mechanism provides new insights into the regulation of COX2 and MMP13 transcription.
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