Dynamic interplay between histone H3 modifications and protein interpreters: emerging evidence for a "histone
1Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Chembiochem : a European Journal of Chemical Biology
|January 19, 2011
Summary
Histone post-translational modifications (PTMs) on histone H3
Area of Science:
- Epigenetics and Molecular Biology
- Chromatin Biology
- Gene Regulation
Background:
- Histone proteins are crucial for DNA organization into chromatin.
- Post-translational modifications (PTMs) on histones regulate chromatin function.
- The histone H3 N-terminus is rich in modifiable residues.
Purpose of the Study:
- To investigate the interplay between histone H3 N-terminal modifications and the binding modules that recognize them.
- To explore the impact of auxiliary modifications on H3K4 methylation binding modules.
- To model how combinatorial PTMs control gene expression.
Main Methods:
- Analysis of histone modification states.
- Study of binding module recognition.
- Case study of androgen-receptor-mediated gene activation.
Main Results:
- Histone PTMs function more like a 'language' than a 'code', emphasizing context.
- Auxiliary modifications (H3R2 methylation, H3T3 phosphorylation, H3T6 phosphorylation) affect H3K4 binding modules.
- A model for combinatorial PTMs controlling gene expression is proposed.
Conclusions:
- The combinatorial nature of histone H3 N-terminal PTMs is critical for gene regulation.
- Context-dependent 'language' of PTMs influences chromatin function.
- Understanding these interactions provides insights into epigenetic control of gene expression.
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,...
02:25Spreading 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
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Writers
The writer is an enzyme that can...
02:41Chromatin Structure Regulates pre-mRNA Processing
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
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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...