Modulation of 14-3-3 interaction with phosphorylated histone H3 by combinatorial modification patterns
Stefan Winter1, Wolfgang Fischle, Christian Seiser
1Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, Vienna, Austria.
Cell Cycle (Georgetown, Tex.)
|April 18, 2008
Summary
Histone modifications regulate genome activity. The 14-3-3 protein binds to phosphorylated histone H3, with binding affinity modulated by additional acetylation marks, impacting gene regulation.
Area of Science:
- Molecular Biology
- Epigenetics
- Chromatin Biology
Background:
- Post-translational modifications (PTMs) of histones are crucial for regulating genome activity.
- Histone H3 phosphorylation is linked to chromatin compaction during mitosis and gene regulation during interphase.
- Specific histone H3 phosphorylation sites, like serine 10, are associated with acetylation events during gene regulation.
Purpose of the Study:
- To investigate the binding interactions between 14-3-3 proteins and histone H3.
- To understand how histone H3 post-translational modifications influence 14-3-3 binding.
- To explore the biological implications of 14-3-3 binding to histone H3.
Main Methods:
- In vitro binding assays to assess protein-protein interactions.
- Analysis of histone H3 phosphorylation and acetylation patterns.
- Characterization of 14-3-3 binding affinity to modified histone H3 peptides.
Main Results:
- 14-3-3 proteins recognize both phosphorylated serine 10 and serine 28 on histone H3.
- 14-3-3 binding to phosphoserine 10 is enhanced by adjacent acetylation at lysine 9 or lysine 14.
- 14-3-3 exhibits a stronger, less modifiable interaction with the histone H3S28 site.
Conclusions:
- Histone H3 phosphorylation and acetylation collectively regulate 14-3-3 binding.
- The differential binding affinities suggest distinct roles for H3S10ph and H3S28ph in gene regulation.
- These interactions may play significant roles in cellular processes governed by histone modifications.
Related Concept Videos
02:32Histone Modification
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
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:32Histone Modification
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
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
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...
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01:12The Nucleosome Core Particle
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
02:10The Nucleosome Core Particle
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...