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Updated: Jun 27, 2026
10:28
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms
Raphael Margueron1, Guohong Li, Kavitha Sarma
1Department of Biochemistry, New York University Medical School, 522 First Avenue, New York, NY 10016, USA.
Molecular Cell
|November 26, 2008
Summary
Mammalian Ezh1 and Ezh2 proteins form Polycomb Repressive Complex 2 (PRC2) but have distinct functions. Ezh2 methylates H3K27, while Ezh1 represses transcription and compacts chromatin independently of methylation.
Area of Science:
- Epigenetics
- Molecular Biology
- Developmental Biology
Background:
- Polycomb group (PcG) proteins maintain gene repression during development.
- The PRC2 complex, including EZH proteins, catalyzes histone H3 lysine 27 di- and trimethylation (H3K27me2/3), a repressive mark.
Purpose of the Study:
- To investigate the distinct repressive roles of mammalian homologs Ezh1 and Ezh2 within the PRC2 complex.
- To understand the functional subfunctionalization of PcG proteins during evolution.
Main Methods:
- Analysis of PRC2 complexes formed by Ezh1 and Ezh2.
- Knockdown experiments to assess global H3K27me2/3 levels.
- In vitro transcription assays using chromatinized templates.
- Electron microscopy for chromatin compaction analysis.
- Expression analysis in aging mouse kidney tissues.
Main Results:
- PRC2-Ezh2 catalyzes H3K27me2/3, with knockdown affecting global levels.
- PRC2-Ezh1 weakly catalyzes H3K27me2/3, and its knockdown does not impact global levels.
- PRC2-Ezh1 robustly represses transcription and compacts chromatin independently of SAM.
- Ezh1 is abundant in nonproliferative organs, while Ezh2 expression correlates with proliferation.
Conclusions:
- Ezh1 and Ezh2 exhibit contrasting repressive roles within PRC2, suggesting subfunctionalization.
- Ezh1 possesses methyltransferase-independent chromatin repression and compaction activities.
- Differential expression patterns of Ezh1 and Ezh2 correlate with cellular proliferation states.
Related Concept Videos
01:01Euchromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
01:01Euchromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
02:25Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
02:32Position-effect Variegation
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.