ディメリックリガンドは,再起動における転写活性化ドメインの役割を定義する
S N Ho1, S R Biggar, D M Spencer
1Department of Pathology, Howard Hughes Medical Institute, Stanford University School of Medicine, California 94305, USA.
Nature
|August 29, 1996
まとめ
生体細胞の遺伝子転写を維持するには,アクティベーターの継続的な存在が必要です. 合成リガンドは,研究および治療における遺伝子転写の制御のための強力なオン・オフスイッチを提供します.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝子規制 遺伝子規制
- 細胞生物学 細胞生物学
背景:
- ユカリオットの転写活性化剤は,前始動複合体を安定させるが,進行中の転写 (再始動) を維持する役割は議論されている.
- インビトロ研究では,開始前複合体の形成後に持続的な転写にアクティベーターが不可欠であるかどうかについて矛盾する結果が得られます.
研究 の 目的:
- 合成リガンドを使用して,生体細胞における遺伝子転写を調節する方法を開発する.
- 生体内における内生性遺伝子転写を維持するために,転写活性化剤の必要性を調査する.
主な方法:
- トランスクリプション活性化ドメインとプロモーターの結合/離散を制御するためのホモジメリックおよびヘテロジメリ化合成リガンドの開発.
- このシステムの適用は,酵母細胞とヒト細胞の両方で内生的な遺伝子転写を調節する.
主要な成果:
- 活化ドメインの継続的な存在が,内生的な遺伝子転写を in vivo で維持するために必要であることを実証した.
- 生体細胞の有効な転写オンオフスイッチとして確立された合成リガンド.
結論:
- 活性化ドメインの継続的な存在は,真核細胞における持続的な遺伝子転写に不可欠である.
- 合成リガンド制御トランスクリプションシステムは,遺伝子発現を制御する実験的および治療的応用のための多用途のツールを提供します.
関連する概念動画
RNA Polymerase II Accessory Proteins
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Eukaryotic Transcription Activators
Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...
Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...


