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Published on: January 26, 2018
Cell cycle-dependent accumulation of histone H3.3 and euchromatic histone modifications in pericentromeric
Kazuto Sugimura1, Yoshiyuki Fukushima, Motoko Ishida
1Laboratory of Molecular and Cellular Biology, Graduate School of Bioresources, Mie University, Tsu, Mie, Japan. k-sugimura@doc.medic.mie-u.ac.jp
Experimental Cell Research
|July 6, 2010
Summary
DNA methylation inhibition in mouse cells alters histone modifications and H3.3 localization. Reduced DNA methylation activates satellite repeat transcription, impacting pericentromeric heterochromatin organization.
Area of Science:
- Epigenetics
- Molecular Biology
- Genomics
Background:
- DNA methylation is a key epigenetic mark regulating gene silencing, especially in heterochromatin.
- The influence of DNA methylation on other chromatin epigenetic features remains debated.
Purpose of the Study:
- To investigate the impact of DNA methylation inhibition on histone modifications and histone H3.3 subnuclear localization.
- To understand the cell cycle-dependent effects of reduced DNA methylation on chromatin structure and gene expression.
Main Methods:
- Utilized a DNA methyltransferase (Dnmt) inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), in mouse fibroblast cells.
- Performed spatio-temporal analysis to track changes in histone modifications and replication timing.
- Examined histone H3.3 deposition in pericentromeric heterochromatin.
Main Results:
- Inhibition of DNA methylation led to de-repression of centromeric and pericentromeric satellite repeats.
- De-repressed pericentromeric chromatin showed enrichment in euchromatic histone modifications (H4 acetylation, H3K4 methylation).
- These modifications accumulated during the second S phase post-treatment, coinciding with an early S phase shift in satellite repeat replication timing. Histone H3.3 was deposited prior to these changes.
Conclusions:
- DNA CpG methylation is crucial for maintaining the structural organization of pericentromeric heterochromatin in mouse cells.
- Reduced DNA methylation triggers cell cycle-dependent alterations in histone modifications and replication timing.
- Histone H3.3 deposition precedes the establishment of euchromatic marks in de-repressed pericentromeric regions.
Related Concept Videos
01:01Euchromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
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...
02:25Spreading 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...
02:32Histone 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,...