ヒストンH3メチル化およびリン酸化によるHP1-クロマチン結合の調節
Wolfgang Fischle1, Boo Shan Tseng, Holger L Dormann
1Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10021, USA. fischlw@rockefeller.edu
Nature
|October 14, 2005
まとめ
ヒストンH3ライシン9メチル化は,ヘテロクロマチンタンパク質1 (HP1) を採用する. しかし,M相中のH3セリン10リン酸化はHP1を排出し,新たな表遺伝子調節機構を明らかにする.
科学分野:
- エピジェネティクスと分子生物学
- 細胞サイクル規則 細胞サイクル規則
- クロマチンのダイナミクス
背景:
- ヒストンH3ライシン9トリメチル化 (H3K9me3) は,ヘテロクロマチンタンパク質1 (HP1) の結合と遺伝子サイレンシングに不可欠です.
- HP1タンパク質は,クロマチンの包装とヘテロクロマチンの形成に不可欠です.
- 細胞サイクル中のHP1ダイナミクスを理解することは,遺伝子調節を理解するための鍵です.
研究 の 目的:
- Mフェーズ中のクロマチンからHP1が解放されるメカニズムを調査する.
- HP1解離の調節におけるヒストン変異の役割を明らかにする.
- ミトーシス中のHP1ダイナミクスに関与する重要な要因を特定する.
主な方法:
- 染色体免疫降水 (ChIP) は,HP1とヒストンの修飾レベルを評価する.
- 細胞サイクル分析とミト細胞染色体調製.
- Aurora B. のような特定のキナーゼの抑制と枯渇.
主要な成果:
- HP1alpha, -beta, -gammaは,安定したH3K9me3レベルにもかかわらず,M相の間にクロマチンから放出されます.
- H3K9me3の隣接するヒストンH3セリン10リン酸化 (H3S10ph) は,HP1.1を異動させるのに十分である.
- オーロラBキナーゼの阻害はHP1解離を防止し,HP1放出のためのH3S10phの必要性を確認します.
結論:
- H3S10phは,M相中のクロマチンからHP1の放出を媒介する,臨時的な重要な変異である.
- 安定したH3K9me3とダイナミックなH3S10phの相互作用は,HP1-クロマチンの相互作用を支配する.
- 隣接する翻訳後の改変のこの組み合わせの読み出しは,細胞サイクル依存遺伝子発現における新しい規制機構を表しています.
関連する概念動画
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.
02:32Histone 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,...