ヒト染色体21を携えたマウスの種別トランスクリプション
Michael D Wilson1, Nuno L Barbosa-Morais, Dominic Schmidt
1Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Science (New York, N.Y.)
|September 13, 2008
まとめ
核環境ではなく,遺伝的配列が,主に同質組織における遺伝子発現を指揮する. マウス細胞におけるヒト染色体21の機能は,配列を示し,転写プログラムを指示する.
科学分野:
- ゲノミクスゲノミクスとは
- 分子生物学は分子生物学である.
- エピジェネティクス エピジェネティクス
背景:
- 転写因子 (TF) は,特定の組織における遺伝子発現を調節する.
- TF結合部位は,種によって急速に異なっており,遺伝子発現に影響を与えます.
- 種間の転写的差異の要因を理解することは極めて重要です.
研究 の 目的:
- 人間の遺伝子配列またはマウスの核環境がヒト染色体21の転写制御を決定するかどうかを判断する.
- 種特有の遺伝子発現におけるシーケンスと環境の役割を調査する.
主な方法:
- ヒト染色体21を携えたアヌプロイドマウス株を活用しました.
- このマウスモデルの肝細胞を分析した.
- マウス核内のヒト染色体21の転写因子結合,転写開始部位,遺伝子発現を評価した.
主要な成果:
- 人間の転写因子結合パターンは,マウス肝細胞内のヒト染色体21に再現されました.
- トランスクリプション開始の里程碑と遺伝子発現は,ヒト肝細胞のパターンを反映した.
- マウスの核環境は,ヒト染色体21のネイティブトランスクリプションプログラムを大きくサポートしました.
結論:
- 同性組織では,遺伝子配列が転写プログラムの主な決定因子である.
- エピジェネティック機構,細胞環境,TFの種間差異は,転写を指揮する上で二次的な役割を果たします.
- これは,保存された組織特異遺伝子発現における内在的な遺伝情報の支配的な役割を強調しています.
関連する概念動画
01:30General Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
02:43Mouse Models of Cancer Study
Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
02:16Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
01:16In-vitro Mutagenesis
To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.