生きている細胞におけるヘテロクロマチンのダイナミクスとメモリ
Nathaniel A Hathaway1, Oliver Bell, Courtney Hodges
1Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell
|June 19, 2012
まとめ
この研究は,H3K9me3のようなヒストンの改変が,細胞世代にわたってどのように伝播し,継承されるかを明らかにしています. これらのエピジェネティックマークは,安定したドメインを形成し,遺伝子発現と細胞記憶に影響を与えます.
科学分野:
- エピジェネティクスと遺伝子調節
- クロマチンの生物学
- 分子細胞生物学 分子細胞生物学
背景:
- 翻訳後のヒストンの改変は,遺伝子調節において重要な役割を果たします.
- 遺伝子発現状態を維持するこれらの改変の伝播と遺伝性のメカニズムは完全に理解されていません.
研究 の 目的:
- 生体細胞におけるクロマチンの改変の動態と遺伝性を調査する.
- ヘテロクロマティックドメインの形成と安定性を支配する運動学を定量的にモデル化する.
主な方法:
- 化学的に誘導された近接を用いたクロマチンインビボアッセイ (CiA) システムの開発.
- HP1αの選択的なリクルートにより,H3K9me3-依存遺伝子の静止がOct4ロカスで誘発される.
- 線維芽細胞と多能細胞におけるクロマチンの変異運動の分析.
主要な成果:
- H3K9me3の改変は,時速約0.18の核個体で対称かつ連続的に増殖し,最大10kbのドメインを形成した.
- 誘発されたヘテロクロマティックドメインは,刺激を除去した後,複数の細胞世代にわたって安定的に継承された.
- 定量モデリングにより,ヒストンのマークとターンオーバーのダイナミクスがドメインの安定性と境界を決定することを明らかにしました.
結論:
- この研究は,ヘテロクロマチン領域の形成と安定性を理解するための定量的な枠組みを提供します.
- ヒストンの改変とターンオーバーの間のダイナミックな競争が表遺伝子遺伝を決定する.
- このモデルは,ゲノム全体のH3K9me3ドメインの行動を予測します.
関連する概念動画
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...
03:17Inheritance of Chromatin Structures
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
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...
02:05Duplication of Chromatin Structure
The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
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.