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Systematic identification of silencers in human cells
Baoxu Pang1,2, Michael P Snyder3
1Department of Genetics, Stanford University, Stanford, CA, USA.
Nature Genetics
|February 26, 2020
Summary
Researchers discovered widespread gene silencers in the human genome that regulate gene expression. These silencers, which repress gene activity, may play a key role in tissue-specific functions and overall human biology.
Area of Science:
- Genomics
- Molecular Biology
- Epigenetics
Background:
- The human genome contains numerous noncoding regions crucial for gene regulation.
- Gene expression is controlled by both activators (enhancers) and repressors (silencers).
- Systematic studies on gene silencers have been limited compared to enhancers.
Purpose of the Study:
- To develop a genome-wide system for identifying silencer regions.
- To characterize the distribution, function, and epigenetic properties of silencers.
- To investigate the role of silencers in gene regulation and human biology.
Main Methods:
- Developed a novel system to identify silencers based on repression of caspase 9 transcription.
- Performed genome-wide analysis to map silencer locations.
- Analyzed epigenetic signatures and associated transcription factors of silencers.
- Investigated silencer interactions at the level of genes, chromosomal domains, and long-range interactions.
- Examined the effect of silencer deletion on drug transporter genes (ABCC2, ABCG2) and chemo-resistance.
Main Results:
- Identified silencer regions as widely distributed throughout the human genome.
- Found that silencers can function in a tissue-specific manner.
- Characterized unique epigenetic signatures and specific transcription factor associations for silencers.
- Demonstrated that silencers can act on multiple genes and influence chromosomal domains and long-range interactions.
- Showed that deletion of silencer regions linked to ABCC2 and ABCG2 genes resulted in chemo-resistance.
Conclusions:
- Tissue-specific gene silencing is a widespread phenomenon in the human genome.
- Silencers play a substantial role in regulating gene expression and human biological processes.
- The findings provide a new perspective on the regulatory landscape of the noncoding genome.
