Heterochromatin protein 1 is extensively decorated with histone code-like post-translational modifications
Gary LeRoy1, John T Weston, Barry M Zee
1Department Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Molecular & Cellular Proteomics : MCP
|July 2, 2009
Summary
This study comprehensively mapped post-translational modifications on Heterochromatin Protein 1 (HP1) isoforms. Findings reveal extensive modifications, including phosphorylation and acetylation, suggesting roles in heterochromatin maintenance.
Area of Science:
- Molecular Biology
- Epigenetics
- Proteomics
Background:
- Heterochromatin Protein 1 (HP1) proteins are crucial for gene silencing and heterochromatin formation.
- HP1s interact with histone H3 methylated at Lys-9.
- Previous studies indicated post-translational modifications (PTMs) of HP1s, but modification sites were not fully identified.
Purpose of the Study:
- To conduct the first comprehensive proteomic analysis of PTMs across all HP1 isoforms (alpha, beta, and gamma).
- To systematically map the sites and types of covalent modifications on HP1 proteins.
Main Methods:
- Utilized tandem mass spectrometry for a large-scale proteomic analysis.
- Investigated all three mammalian HP1 isoforms.
Main Results:
- All HP1 isoforms (alpha, beta, gamma) exhibit extensive PTMs, including phosphorylation, acetylation, methylation, and formylation.
- Several modification sites were found to harbor multiple types of PTMs simultaneously.
- Many identified PTMs are located within the chromo- and chromoshadow domains of HP1 proteins.
Conclusions:
- This study provides the first systematic mapping of abundant covalent modification sites on HP1 isoforms.
- The extensive modifications, particularly in functional domains, suggest a significant role in regulating HP1 interactions and functions.
- These findings lay the groundwork for future research into the necessity of these PTMs for heterochromatin maintenance and other nuclear processes.
Related Concept Videos
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The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
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Acetylation
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02:32Histone Modification
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Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
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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...
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02:38Heterochromatin
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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...
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02:25Spreading of Chromatin Modifications
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01:01Euchromatin
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