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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Genome-wide chromatin remodeling modulates the Alu heat shock response
1Department of Chemistry, University of California, Davis, CA 95616-8535, USA.
Heat shock causes a temporary increase in Alu RNA and opens chromatin structure in Hela cells. This genome-wide chromatin remodeling, independent of transcription, suggests a role for chromatin dynamics in regulating repetitive elements like SINEs.
Area of Science:
- Molecular Biology
- Genetics
- Epigenetics
Background:
- Heat shock response involves transient expression of heat shock proteins.
- Repetitive elements like Alu, alpha satellite, and LINE1 constitute a significant portion of the genome.
- Chromatin structure plays a crucial role in gene regulation.
Purpose of the Study:
- To investigate the effect of heat shock on Alu RNA levels and chromatin accessibility.
- To determine if heat shock induces genome-wide chromatin remodeling.
- To explore the role of chromatin dynamics in the regulation of repetitive elements.
Main Methods:
- Hela cells were subjected to heat shock and recovery.
- Alu RNA levels were measured.
- Chromatin accessibility to restriction enzymes was assessed for Alu, alpha satellite, and LINE1 sequences.
- Nucleosome positioning was inferred from accessibility data.
Main Results:
- Heat shock recovery led to a transient increase in Alu RNA levels, paralleling heat shock protein mRNA expression.
- Chromatin accessibility to restriction enzymes increased transiently for Alu, alpha satellite, and LINE1 sequences.
- Heat shock induced genome-wide chromatin remodeling independent of transcription.
- Increased accessibility suggested nucleosome position scrambling rather than linker lengthening.
Conclusions:
- Heat shock triggers a stress response involving transient Alu RNA upregulation and significant chromatin remodeling.
- Chromatin opening and re-closing appear to regulate the Alu stress response.
- Genome-wide chromatin remodeling during heat shock is independent of transcriptional changes.
- Chromatin structure and dynamics may explain key features of SINE regulation, including their dispersion and high copy number.
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