エウテリアン哺乳類は,発達過程でX染色体不活性化を開始するためにさまざまな戦略を使用します
Ikuhiro Okamoto1, Catherine Patrat, Dominique Thépot
1Mammalian Developmental Epigenetics Group, Institut Curie, CNRS UMR 3215, INSERM U934, Paris 75248, France.
Nature
|April 8, 2011
まとめ
雌性哺乳類は,X染色体不活性化 (XCI) を用いて,遺伝子用量補償を行う. ネズミと異なり,ウサギとヒトはXCIを後に開始し,XISTのアップレギュレーションが染色体サイレンスに先行し,哺乳類の多様な発達戦略を明らかにします.
科学分野:
- 発達生物学 発達生物学とは
- 遺伝学 遺伝学とは
- 哺乳類の胚形成について
背景:
- X染色体不活性化 (XCI) は,雌性哺乳類の性別間のX関連遺伝子発現を均等にします.
- ネズミでは,父親のXCIはXISTRNAを介してインプリントされ,内側の細胞質量に逆転し,その後,エピブラスト細胞のランダムなXCIが続きます.
研究 の 目的:
- ウサギとヒトにおけるX染色体不活性化 (XCI) 開始戦略を,マウスにおける戦略と比較して調査する.
- 異なるエウテリアン哺乳類における早期胚形成におけるXISTRNAインプリントとアップレギュレーションの役割を明らかにする.
主な方法:
- XIST遺伝子発現とX染色体不活性化パターンの比較分析.
- ウサギとヒトにおける胚の発達に関する研究で,ブラストシストの段階に焦点を当てています.
- XIST RNAインプリントとXCIタイミングとの相関を調査する.
主要な成果:
- ウサギとヒトはマウスと比較して,XCIの開始が遅れているが,XISTはインプリントにはならない.
- XISTのアップレギュレーションは,ウサギとヒトの胚のX染色体の両方に発生し,内側の細胞質量の中にも発生します.
- ウサギでは,XISTのアップレギュレーションにより,バイアレルXCIが誘発され,ヒトでは,XISTのアップレギュレーションにもかかわらず,XCIの開始は,芽細胞の段階を超えて遅延されます.
結論:
- 哺乳類のX染色体不活性化 (XCI) 調節は,特に初期の胚形成において,著しい多様性を示しています.
- XISTの役割を含むXCI開始のタイミングとメカニズムは,エウテリアン種によってかなり異なります.
- 非活性X染色体の選択は,ウサギとヒトのXIST上流調節の下流で発生し,マウスモデルとは異なる.
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...
Dosage Compensation
In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
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...
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...


