インテグレーターによる転写規制の構造的基礎
Isaac Fianu1, Ying Chen1, Christian Dienemann1
1Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Science (New York, N.Y.)
|November 11, 2021
まとめ
インテグレータータンパク質・フォスファタゼ2A複合体
科学分野:
- 分子生物学
- 遺伝子規制
- 生物化学
背景:
- トランスクリプションの終結は遺伝子調節に不可欠です.
- インテグレーター・コンプレックスとタンパク質・フォスファタゼ2A (PP2A) は,この過程の重要な要素です.
- RNAポリメラーゼII (Pol II) との相互作用を理解することは不可欠です.
研究 の 目的:
- トランスクリプションの構造的基礎を明らかにする.
- 人体インテグレーターPP2AとポーズされたPolIIを含むプリターミネーション複合体を視覚化します.
- Integrator-PP2AがPol IIの活性とRNAの分裂をどのように調節するかを理解する.
主な方法:
- プリターミネーション複合体の構造を決定するX線結晶学.
- タンパク質とタンパク質と核酸の相互作用を分析する生化学的測定法
主要な成果:
- 構造は,インテグレーターがPol II,DSIF,およびNELFをどのように結合するか,延長因子を除外します.
- インテグレーターはPP2AをPol IIの脱酸化に配置し,延長を阻害する.
- インテグレーターエンドヌクレアゼは,Pol II活性部位の近くの新生RNAを割って,終了を容易にします.
結論:
- Integrator-PP2A複合体は,構造的および酵素的メカニズムによって直接転写終結を媒介する.
- これは 転写が正確に停止される方法の 分子的な理解を 提供します
- この発見は,変異性転写を含む疾患の潜在的な治療目標についての洞察を提供します.
関連する概念動画
02:36RNA Polymerase II Accessory Proteins
9.8K
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...
9.8K
02:04Co-activators and Co-repressors
7.7K
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...
7.7K
02:42Eukaryotic Transcription Activators
11.4K
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...
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
11.4K
02:16Transcription Factors
79.2K
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...
79.2K
02:23Master Transcription Regulators
7.2K
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...
7.2K
02:40The Eukaryotic Promoter Region
17.1K
The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
17.1K