X不活性化センターの規制の空間分割
Elphège P Nora1, Bryan R Lajoie, Edda G Schulz
1Institut Curie, 26 rue d'Ulm, Paris F-75248, France.
Nature
|April 13, 2012
まとめ
研究者は5Cと顕微鏡を用いてマウスX無活性化センター (Xic) の空間的組織をマッピングした. 彼らはXist発現と遺伝子クラスタを調節するトポロジカルアソシエイトドメイン (TADs) を発見し,哺乳類の染色体構造の新たな原理を明らかにした.
科学分野:
- ゲノミクスゲノミクスとは
- 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.
背景:
- ユカリオットの転写調節には,長距離の要素とゲノムの文脈が含まれています.
- マウスX無活性化センター (Xic) は,Xistトランスクリプトを通じてX染色体無活性化 (XCI) を制御する.
- Xist 調節のための Xic 配列の完全な範囲は完全に理解されていません.
研究 の 目的:
- Xic,Xistを含むXicの4.5Mbの領域の空間的組織を分析する.
- Xist規制とXCIにおけるトポロジカル・アソシエイトドメイン (TAD) の役割を理解する.
- Xic. 内の新しい規制要素を特定する.
主な方法:
- 染色体コンフォームキャプチャカーボンコピー (5C) テクノロジー.
- 超解像度顕微鏡 超解像度顕微鏡 超解像度顕微鏡
- エピジェネティック変異と遺伝子発現パターンの分析.
主要な成果:
- 細胞分化とX染色体の状態にわたって存在するXic内の離散的トポロジカル関連ドメイン (TADs) の発見.
- TADは,H3K27me3 / H3K9me2ブロックやラミナ関連ドメインなどの表遺伝的特徴と一致しますが,それとは独立しています.
- TADがXist/Tsixユニットなどの規制要素を空間的に分離し,TAD境界の破壊が転写の誤調に繋がることを実証した.
- Tsixの新型遠隔制御領域を特定し,長い間隔RNA,Linx.を産生する.
結論:
- TADは,哺乳類の染色体におけるシス調節構造の基本的原理を表しています.
- TADによるXicの空間的組織は,XistとXCIの正確な調節に不可欠です.
- この研究は,X不活性化センターのさらなる遺伝子解剖のための基礎を提供します.
関連する概念動画
X-Inactivation
The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
X-inactivation
The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
Inheritance 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...
Heterochromatin
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...
Euchromatin
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...
Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...


