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Updated: Jul 14, 2026
Chromatin Immunoprecipitation (ChIP) of Histone Modifications from Saccharomyces cerevisiae
Published on: December 29, 2017
The fission yeast Jmj2 reverses histone H3 Lysine 4 trimethylation
Maite Huarte1, Fei Lan, Taesoo Kim
1Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Abstract:
Histone methylation regulates transcription, chromatin structure, and the epigenetic state of the cell. Recent studies identified the JmjC domain as a catalytic module for histone demethylation. Schizosaccharomyces pombe contains seven JmjC proteins, but it was unclear whether any of them functioned as histone demethylases. In this report, we show that the JmjC protein Jmj2, which is evolutionarily conserved from yeast to human, reversed trimethylated H3-Lys-4 to di- and mono-but not unmethylated products. Overexpression of Jmj2 but not a catalytically inactive mutant reduced H3-Lys-4 trimethylation levels in vivo and suppressed the toxicity caused by overexpression of the H3-Lys-4-me3-binding protein Yng1 in budding yeast. Genome-wide analysis showed that the loss of jmj2 was associated with an increase in the H3-Lys-4-me3 signal, which was enriched near the transcriptional start sites and the coding regions. At the mating-type locus, the loss of jmj2 or substitution of jmj2 with a catalytically inactive form is correlated with increased reporter gene transcription and H3-Lys-4-me3/2 levels, suggesting that Jmj2 and its demethylase activity may play a role in heterochromatin biology. Our findings identified a novel S. pombe histone demethylase with specificity toward di- and trimethylated histone H3-Lys-4 and a possible role in heterochromatin regulation.
Insights
The Jmj2 protein in Schizosaccharomyces pombe acts as a histone demethylase, specifically removing trimethyl marks from H3-Lys-4. This epigenetic regulation is crucial for gene transcription and heterochromatin function.
Area of Science:
- Epigenetics
- Molecular Biology
- Yeast Genetics
Background:
- Histone methylation is a key epigenetic regulator of cellular processes.
- The JmjC domain is known for catalyzing histone demethylation.
- The function of seven JmjC proteins in Schizosaccharomyces pombe, including histone demethylase activity, remained largely uncharacterized.
Purpose of the Study:
- To identify and characterize a novel histone demethylase in Schizosaccharomyces pombe.
- To investigate the enzymatic activity and in vivo function of the JmjC protein Jmj2.
- To explore the role of Jmj2 in regulating H3-Lys-4 methylation and heterochromatin biology.
Main Methods:
- Biochemical assays to determine the demethylase activity of Jmj2 on trimethylated H3-Lys-4.
- In vivo studies involving overexpression of Jmj2 and its mutants in budding yeast.
- Genome-wide analysis to assess the impact of jmj2 loss on H3-Lys-4 methylation patterns.
- Reporter gene assays at the mating-type locus to evaluate transcriptional changes.
Main Results:
- Jmj2 demonstrated specific demethylase activity, converting trimethylated H3-Lys-4 to di- and monomethylated forms.
- Overexpression of Jmj2 reduced H3-Lys-4 trimethylation levels in vivo and rescued toxicity associated with Yng1 overexpression.
- Loss of jmj2 led to increased H3-Lys-4 trimethylation, particularly near transcriptional start sites.
- Reduced jmj2 function correlated with increased reporter gene transcription and H3-Lys-4 methylation at the mating-type locus.
Conclusions:
- Jmj2 is identified as a novel histone demethylase in S. pombe with specificity for di- and trimethylated H3-Lys-4.
- Jmj2 plays a significant role in regulating H3-Lys-4 methylation levels.
- The findings suggest a role for Jmj2-mediated demethylation in the regulation of heterochromatin.
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