ヒストンH3.3は,胚性幹細胞における内生的なレトロウイルスエレメントサイレンシングに必要である
Simon J Elsässer1,2, Kyung-Min Noh3, Nichole Diaz3
1MRC Laboratory of Molecular Biology, Francis Crick Ave, Cambridge, CB2 0QH, United Kingdom.
Nature
|May 5, 2015
まとめ
ヒストン変異種H3.3は,胚性幹細胞における内生性レトロウイルス要素 (ERV) のレトロトランスポジションを制御する. その堆積はKAP1とESETとリンクし,ERVを静止し,ゲノム不安定性を防ぐユニークなヘテロクロマチン状態を確立します.
科学分野:
- ゲノミクスとエピジェネティクス
- 分子生物学は分子生物学である.
- 哺乳類ゲノム規制について
背景:
- 移植可能な元素 (TEs) は哺乳類のゲノムの大部分を構成し,遺伝的多様性だけでなく,ゲノム不安定性にも貢献しています.
- TEsのサブセットである内生レトロウイルス要素 (ERVs) は,マウス胚性幹細胞のESETとKAP1経由でヒストンH3ライシン9トリメチル化 (H3K9me3) によって通常静止されます.
研究 の 目的:
- マウスの胚性幹細胞におけるERVの調節と静止におけるヒストン変異体H3.3の役割を調査する.
- H3.3の堆積,H3K9me3,およびERVの逆転移の関係を解明する.
主な方法:
- 染色体免疫降水 (ChIP) は,ERVでH3.3,H3K9me3,KAP1,ATRX,およびDAXXの濃縮を評価する.
- H3.3 削除または枯渇後のERVおよび隣接遺伝子発現の分析.
- 特定のERVファミリー (ETn/MusD,IAP) のレトロトランスポーゼーション率の評価.
主要な成果:
- ヒストン変種H3.3は,特定のERV (クラスI,クラスII,ETn/MusD,IAP) で濃縮され,堆積はATRX/DAXXチャペロン複合体に依存しています.
- DAXX,H3.3,KAP1のERVへの誘導は相互依存しており,ESET媒介のH3K9me3に先行し,H3.3をERVのヘテロクロマチン形成と結びつける.
- H3.3の枯渇は,ERVでH3K9me3を減少させ,隣接する遺伝子の減圧を引き起こし,IAPの逆転移を増加させます.
結論:
- H3.3とH3K9me3の両方によって特徴づけられる新しいヘテロクロマチン状態がERVsで特定されています.
- H3.3は,ERVの逆転移を制御し,胚性幹細胞のゲノム安定性を維持する上で重要な役割を果たします.
- H3.3媒介サイレンシングの失調は,異常な遺伝子発現と潜在的なゲノム不安定性に寄与する.
さらに関連する動画
13:47Lentiviral Vector Platform for the Efficient Delivery of Epigenome-editing Tools into Human Induced Pluripotent Stem Cell-derived Disease Models
Published on: March 29, 2019
10.5K
10:10Retroviral Scanning: Mapping MLV Integration Sites to Define Cell-specific Regulatory Regions
Published on: May 28, 2017
8.9K
関連する概念動画
03:18Non-LTR Retrotransposons
14.1K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
14.1K
03:08LTR Retrotransposons
20.6K
LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
20.6K
01:32Chromatin Modification in iPS Cells
2.3K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
2.3K
02:33Retroviruses
16.0K
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
16.0K
01:14Maintenance of the ES Cell State
2.8K
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
2.8K
01:26Size and Structure of Viral Genomes
1.2K
Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
1.2K