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H3K36 methylation antagonizes PRC2-mediated H3K27 methylation
Wen Yuan1, Mo Xu2, Chang Huang1
1From the State Key Laboratory of Plant Physiology and Biochemistry, College of Biological Sciences, China Agricultural University, Beijing 100094, China,; the National Institute of Biological Sciences, Beijing 102206, China.
The Journal of Biological Chemistry
|January 18, 2011
Summary
Histone H3K36 methylation restrains the spread of H3K27 methylation by the PRC2 complex, a key regulator of gene silencing. Ash1 protein is identified as an H3K36 dimethylase, further supporting this antagonistic relationship.
Area of Science:
- Epigenetics and transcriptional regulation
- Histone modifications
- Chromatin biology
Background:
- Polycomb Repressive Complex 2 (PRC2) mediates H3K27 methylation, crucial for gene silencing and developmental processes.
- H3K27 methylation spread can establish and maintain repressive chromatin environments.
- Antagonistic chromatin components are vital for limiting PRC2 activity and Polycomb silencing.
Purpose of the Study:
- To investigate the role of H3K36 methylation in antagonizing PRC2-mediated H3K27 methylation.
- To characterize the enzymatic activity of Ash1 protein in relation to H3K36 methylation.
- To understand the interplay between H3K36 and H3K27 methylation in chromatin regulation.
Main Methods:
- Analysis of H3K27 and H3K36 methylation patterns in HeLa cells.
- Biochemical assays to assess PRC2 activity on H3K36 methylated substrates.
- Enzymatic assays to determine Ash1's histone methyltransferase specificity.
Main Results:
- H3 histones unmethylated at K36 are typically methylated at K27, except for newly synthesized H3.
- H3K27 trimethylation (K27me3) rarely co-occurs with H3K36 dimethylation (K36me2) or trimethylation (K36me3) on the same histone.
- PRC2 activity is significantly inhibited by pre-existing H3K36 methylation on nucleosomal substrates.
- Ash1 protein functions as an H3K36-specific dimethylase, not an H3K4 methylase.
Conclusions:
- H3K36 methylation acts as a direct antagonist to PRC2-mediated H3K27 methylation spread.
- Ash1's role as an H3K36 dimethylase supports its function in counteracting Polycomb silencing.
- The interplay between H3K36 and H3K27 methylation is a critical mechanism for fine-tuning transcriptional states.
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