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Published on: August 1, 2017
Substrate preferences of the EZH2 histone methyltransferase complex
Cyrus Martin1, Ru Cao, Yi Zhang
1Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599, USA.
The Journal of Biological Chemistry
|January 25, 2006
Summary
Linker histone H1 and chromatin structure significantly influence the EZH2 complex's histone H3 methylation activity. The EZH2 complex prefers dinucleosomes, and H1 stimulation requires higher-order chromatin structures.
Area of Science:
- Epigenetics and Molecular Biology
- Chromatin Biology
- Enzymology
Background:
- Histone methylation, particularly H3K27 methylation by the EZH2 complex, is crucial for gene regulation, including homeotic gene silencing and X chromosome inactivation.
- Understanding the substrate specificity of the EZH2 complex is key to elucidating its role in epigenetic control.
Purpose of the Study:
- To characterize the substrate preferences of the EZH2 histone methyltransferase complex.
- To investigate the roles of linker histone H1 and chromatin structure in modulating EZH2 activity.
- To examine the impact of EED isoforms on EZH2 substrate specificity.
Main Methods:
- Utilized a reconstituted chromatin and enzyme system for in vitro characterization.
- Assessed EZH2 activity using mononucleosomes, dinucleosomes, and oligonucleosomes as substrates.
- Reconstituted EZH2 complexes with different Embryonic Ectoderm Development (EED) isoforms.
Main Results:
- Linker histone H1 incorporation into nucleosomes stimulates EZH2 activity towards histone H3.
- The EZH2 complex shows a strong preference for dinucleosomes over mononucleosomes.
- H1-mediated stimulation of H3 methylation requires dinucleosome or oligonucleosome substrates.
- Different EED isoforms did not alter the substrate preference or specificity of the EZH2 complex.
Conclusions:
- Linker histone H1 and higher-order chromatin structures (dinucleosomes/oligonucleosomes) are critical determinants of EZH2 substrate preference.
- Chromatin organization plays a significant role in regulating EZH2 methyltransferase activity.
- EED isoforms do not appear to significantly influence EZH2 substrate specificity in this system.
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