Genome-wide histone modifications: gaining specificity by preventing promiscuity
Fred van Leeuwen1, Daniel E Gottschling
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
Current Opinion in Cell Biology
|December 11, 2002
Summary
Histone modifications on nucleosomes can create specific chromatin domains. Genome-wide histone modifications prevent non-specific protein binding, ensuring proper chromosome organization.
Area of Science:
- Molecular Biology
- Epigenetics
- Chromatin Biology
Background:
- Nucleosomes, the basic units of chromatin, are composed of four core histone proteins.
- Histone proteins contain over 20 residues susceptible to post-translational modifications (PTMs) like methylation, acetylation, ubiquitination, and phosphorylation.
- These PTMs are hypothesized to regulate non-histone protein recruitment to chromatin, influencing gene expression and genome structure.
Purpose of the Study:
- To investigate the role of histone modifications in chromatin organization.
- To explore how specific patterns of histone modifications contribute to the formation of distinct chromatin domains.
- To examine the impact of genome-wide histone modifications on the binding of chromatin proteins.
Main Methods:
- Analysis of post-translational modifications on histone proteins.
- Investigating the relationship between histone modification patterns and chromatin domain formation.
- Assessing the effect of genome-wide histone modifications on non-specific protein binding to chromatin.
Main Results:
- Specific patterns of histone modifications are associated with the creation of distinct chromatin domains.
- Genome-wide histone modifications reduce the non-specific binding of chromatin proteins involved in gene silencing.
- This reduction in promiscuous binding prevents the titration of silencing proteins away from their target sites.
Conclusions:
- Histone modifications play a crucial role in establishing specific chromatin domains and overall chromosome organization.
- Preventing non-specific protein binding through genome-wide histone modifications is essential for maintaining chromatin specificity.
- The precise regulation of protein-chromatin interactions by histone modifications is fundamental for cellular function.
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,...
02:25Spreading 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...
02:32Histone 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,...
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...