Oct-4とE1Aとの結びつき:胚性幹細胞における遺伝子調節への影響
H R Schöler1, T Ciesiolka, P Gruss
1Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, Göttingen, Federal Republic of Germany.
Cell
|July 26, 1991
まとめ
Oct-4およびE1Aタンパク質は,距離に関係なく遺伝子転写を活性化することができます. その比率は効率にとって極めて重要で,E1Aが多能細胞におけるOct-4への橋渡し因子として作用することを示唆している.
科学分野:
- 分子生物学は分子生物学である.
- 発達生物学 発達生物学とは
- 遺伝子規制 遺伝子規制
背景:
- Oct-4は,初期のマウス胚の多能原始細胞における重要な転写因子である.
- エクトピックOct-4を持つ分化細胞におけるディスタル遺伝子の活性化には,追加の要因が必要である.
研究 の 目的:
- 基礎転写機構の活性化におけるOct-4とE1Aの十分性を調査する.
- 転写活性化におけるOct-4とE1A比の役割を決定する.
- Oct-4媒介による転写活性化のメカニズムを解明する.
主な方法:
- 細胞系におけるOct-4とE1Aの共発現.
- 距離に関係なく遺伝子の活性化の分析.
- タンパク質とタンパク質の相互作用とドメインの要件を研究するための生化学的測定法.
主要な成果:
- Oct-4とE1Aは,距離に関係なく基礎転写の活性化に十分である.
- Oct-4とE1Aの比率は極めて重要で,いずれかの要因のレベルが高くなった場合,効率が低下する.
- アクティベーションには,Oct-4にトランザクションドメインと,Oct-4に結合するE1Aの保存ドメイン3が必要です.
- E1Aは,Oct-4と基礎転写開始複合体との間の橋渡し因子として作用します.
結論:
- E1Aは,Oct-4の基礎転写機構との相互作用を容易にする.
- E1Aのような因子が多能細胞のOct-4を橋渡しするモデルが提案されています.
- この発見は,多能性と遺伝子発現の規制メカニズムに光を当てています.
関連する概念動画
Embryonic Stem Cells
Embryonic stem (ES) cells are undifferentiated pluripotent cells, meaning they can produce any cell type in the body. This gives them tremendous potential in science and medicine since they can generate specific cell types for use in research or to replace body cells lost due to damage or disease.
Combinatorial Gene Control
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
Embryonic Stem Cells
Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...
Maintenance of the ES Cell State
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...
Somatic to iPS Cell Reprogramming
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012 for this...
Methods of Nuclear Reprogramming
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for injury repair.


