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Lid2は,ヘテロクロマチンとエウクロマチンのH3K4とH3K9メチル化を調整するために必要です
Fei Li1, Maite Huarte, Mikel Zaratiegui
1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. feili@nature.berkeley.edu
Cell
|October 30, 2008
まとめ
JmjCドメインのタンパク質Lid2はヒストンH3リジン-4 (H3K4) 脱メチラーゼとして作用し,ヘテロクロマチン形成と遺伝子静止に不可欠です. Lid2は,H3K4の脱メチル化とH3K9のメチル化を結びつけ,クロマチンの調節を調整する.
科学分野:
- エピジェネティクス エピジェネティクス
- クロマチンの生物学
- 分子生物学は分子生物学である.
背景:
- ヒストンのメチル化パターン,特にH3K9とH3K4のメチル化パターンは,それぞれヘテロクロマチンとエウクロマチンを定義するために重要である.
- これらの変異は,クロマチンの構造とエウカリオットの遺伝子発現の調節を左右する.
研究 の 目的:
- S. pombe.におけるJmjCドメインタンパク質Lid2の機能を特定する.
- ヒストンのメチル化を調節するLid2の役割とそのクロマチンの構造への影響を解明する.
主な方法:
- デメチラゼとしてのLid2の酵素活性を決定する生化学的測定.
- ヘテロクロマチンの形成と静止におけるLid2機能の遺伝子解析.
- Lid2,Clr4,およびDos1/Clr8-Rik1複合体間のタンパク質とタンパク質の相互作用を調査する.
主要な成果:
- Lid2は,ヘテロクロマチンのH3K4低メチル化に責任を負うトリメチルH3K4デメチラーゼとして特定されました.
- Lid2は,Dos1/Clr8-Rik1複合体を通じて,H3K9メチルトランスファーゼClr4と物理的に,機能的に相互作用する.
- Lid2のJmjCドメインの破壊は,ヘテロクロマチン欠陥とsiRNAの枯渇を引き起こし,Lid2の過剰発現は静止を強化しました.
- Lid2は,ユークロマチンのH3K4およびH3K9メチル化のクロス調節にも必要である.
結論:
- Lid2は,適切なヘテロクロマチンの形成と遺伝子サイレンシングのために,H3K4とH3K9のメチル化を調整する二重の役割を果たしています.
- この発見は,H3K4脱メチル化とH3K9メチル化との間のメカニズム的な関連性を明らかにし,協調された表遺伝子調節を強調しています.
- ユークロマチン内のLid2の活動は,他のヒストン修飾酵素とのダイナミックな相互作用によって調節される可能性が高い.
関連する概念動画
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,...
01:01Euchromatin
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...
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...
02:32Histone 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,...