ヒストンH3R2のPRMT6によるメチル化と,MLL複合体によるH3K4のメチル化は,相互排斥的である
Ernesto Guccione1, Christian Bassi, Fabio Casadio
1Department of Experimental Oncology, European Institute of Oncology (IEO), IFOM-IEO Campus, Milan 20139, Italy.
Nature
|September 28, 2007
まとめ
ヒストンのメチル化マーク,特にH3R2me2aとH3K4me3は,遺伝子発現を敵対的に調節する. PRMT6酵素はH3R2me2aを媒介し,H3K4me3.3を含む活性プロモーターから不足している.
科学分野:
- エピジェネティクス エピジェネティクス
- 分子生物学は分子生物学である.
- ゲノミクスゲノミクスとは
背景:
- ユーカリオットのゲノムにはユークロマティック・ドメインとヘテロクロマティック・ドメインがあり,ヒストンの翻訳後の改変 (マーク) によって区別される.
- これらのマークは,特にプロモーター領域では,クロマチンの機能状態を定義し,複雑な相互作用によって調節されます.
- 以前の研究では,ヒトのプロモーターにおけるヒストンH3アルギニン2非対称二甲基化 (H3R2me2a) とH3ライシン4二および三甲基化 (H3K4me2,H3K4me3) の対照的相関が認められた.
研究 の 目的:
- H3R2二メチル化を触媒化するPRMT6の役割を調査する.
- H3R2me2aとH3K4メチル化との規制関係を解明する.
- 哺乳類のゲノムにおけるH3R2me2aの分布と調節を理解する.
主な方法:
- H3R2.2に対するPRMT6の活性を決定するインビトロ酵素測定法.
- 世界的なH3R2me2aレベルに対するPRMT6のコントロールを評価するためのインビボ試験.
- クロマチン免疫降水法 (ChIP) は,ヒトの遺伝子におけるH3R2me2aとH3K4me3の分布をマッピングする.
主要な成果:
- PRMT6は,H3R2二メチル化をインビトロで触媒化し,そのレベルをインビヴォで制御する酵素として特定されました.
- H3K4me3はPRMT6によるH3R2メチル化を阻害し,H3R2me2aはH3K4メチル化とMLLファミリー複合体の結合を阻害することが判明しました.
- H3R2me2aは遺伝子体と3'末端で濃縮されたが,H3K4me3の存在と一致して,活性プロモーターから選択的に枯渇した.
結論:
- H3R2とH3K4メチル化の間には相互の敵対的な関係がある.
- PRMT6およびMLLファミリー複合体を含むこの対抗性は,活性哺乳類のプロモーターにおける特定のH3K4トリメチル化パターンに寄与する.
関連する概念動画
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,...
02:38Heterochromatin
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...
02:41Chromatin 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...
The chromatin structure, especially...
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...
02:32Position-effect Variegation
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.