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関連する概念動画

General Transcription Factors01:30

General Transcription Factors

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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...
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Transcription Factors02:16

Transcription Factors

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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...
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RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

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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...
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Cis-regulatory Sequences02:02

Cis-regulatory Sequences

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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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Co-activators and Co-repressors02:04

Co-activators and Co-repressors

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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...
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Master Transcription Regulators02:23

Master Transcription Regulators

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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...
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HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
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人間のシーケンス固有の転写因子の位置依存機能

Sascha H Duttke1, Carlos Guzman2, Max Chang2

  • 1School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA. sascha.duttke@wsu.edu.

Nature
|July 17, 2024
PubMed
まとめ

転写因子 (TF) の結合部位と転写開始部位 (TSS) の位置は遺伝子調節を左右する. この位置的依存性は,同様のTF結合部位が多様な遺伝子発現パターンを生成し,病気に寄与する方法を説明します.

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Author Spotlight: An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations
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Real-time Analysis of Transcription Factor Binding, Transcription, Translation, and Turnover to Display Global Events During Cellular Activation
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科学分野:

  • ゲノミクスと分子生物学
  • 遺伝子調節と転写

背景:

  • プロモーターや強化剤のような規制要素には,転写因子 (TF) の結合部位が含まれています.
  • これらの部位が遺伝子発現を 暗号化する仕組みを理解することは 遺伝子調節と病気の研究に不可欠です
  • 同様のTF結合部位の配置は,異なる遺伝子発現結果につながる可能性があります.

研究 の 目的:

  • 遺伝子調節における転写開始部位 (TSS) に関するTF結合部位の役割を調査する.
  • TF結合部位の空間的構成がトランスクリプションの開始にどのように影響するかを決定する.
  • DNA 配列の変異が転写変異と病気に寄与するメカニズムを解明する.

主な方法:

  • 個々のTSSの観点から遺伝子調節の分析.
  • 自然遺伝的多様性,内生性TFタンパク質レベルの乱れ,そして大量並列レポーター測定を用いた.
  • 位置偏好を特定するために,TSSに対するTF結合場所の発生を分析した.

主要な成果:

  • トランスクリプション開始に対するTF結合の効果は位置に依存することを実証した.
  • TSSに対して非常に優遇的な位置づけを持ついくつかのTF拘束モチーフを特定しました.
  • TFsは,TSSに対する正確な位置に基づいて,転写の開始を活性化または抑制することが示されています.

結論:

  • TF結合部位の位置と距離は,共同で転写開始部位と頻度を導く.
  • 同様のTF結合部位の配列が,空間的構成に基づいて異なった遺伝子調節結果を生成する方法を明らかにした.
  • ゲノム制御情報を解読し,病気のメカニズムを理解する上でTSSデータの重要な役割を強調した.