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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Histone methylation by PRC2 is inhibited by active chromatin marks
Frank W Schmitges1, Archana B Prusty, Mahamadou Faty
1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
Molecular Cell
|May 10, 2011
Summary
Polycomb repressive complex 2 (PRC2) activity is inhibited by active histone marks like H3K4me3 and H3K36me2/3. This ensures PRC2 avoids repressing transcriptionally active chromatin, maintaining cellular function.
Area of Science:
- Epigenetics and Gene Regulation
- Chromatin Biology
- Molecular Mechanisms of Transcription
Background:
- Polycomb repressive complex 2 (PRC2) establishes gene silencing via H3K27me3.
- Understanding how PRC2 interacts with active chromatin marks is crucial for gene regulation.
Purpose of the Study:
- To investigate the molecular mechanisms by which active histone modifications modulate PRC2 activity.
- To elucidate how PRC2 distinguishes between active and inactive chromatin.
Main Methods:
- Biochemical assays to study PRC2 interaction with histone peptides.
- Structural analysis of the PRC2 Nurf55-Su(z)12 submodule.
- Cross-species conservation studies.
Main Results:
- Identified the molecular basis for H3 N-terminus recognition by the PRC2 Nurf55-Su(z)12 submodule.
- Demonstrated that H3K4me3 and H3K36me2/3 allosterically inhibit PRC2 activity.
- Showed this inhibition is conserved across humans, mice, and flies, preventing PRC2 from acting on active chromatin.
Conclusions:
- Active chromatin marks (H3K4me3, H3K36me2/3) directly inhibit PRC2, making active regions refractory to H3K27 trimethylation.
- PRC2 autonomously templates H3K27me3 on repressive regions while avoiding active domains.
- Plant PRC2 inhibition can be modulated by altering the Su(z)12 subunit.
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01:01Euchromatin
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01:46Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
01:37Epigenetic Regulation
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