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Transcription Factors02:16

Transcription Factors

82.2K
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...
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Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

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Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
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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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Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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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...
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Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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Conserved Binding Sites01:49

Conserved Binding Sites

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Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
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High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy
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baal-nfは転写因子結合親和性を低下させるモチーフ破壊バリアントを特定する

Breeshey Roskams-Hieter1,2, Øyvind Almelid3, Chris P Ponting4

  • 1Institute of Genetics and Cancer, MRC Human Genetics Unit, Western General Hospital, University of Edinburgh, Edinburgh, EH4 2XU, UK. b.j.roskams-hieter@sms.ed.ac.uk.

Genome biology
|January 12, 2026
PubMed
まとめ
この要約は機械生成です。

研究者らは、転写因子結合を変化させることによりヒト形質を変化させる可能性のある1,935の遺伝子バリアントを特定した。この発見は、ヒト変異の遺伝的基礎を理解するのに役立つ。

キーワード:
対立遺伝子特異的結合対立遺伝子不均衡ChIPシーケンシングモチーフ転写因子

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06:38

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科学分野:

  • 遺伝学
  • ゲノム科学
  • 分子生物学

背景:

  • ヒト形質は、遺伝的変異を示す。これは、遺伝子制御領域内の転写因子結合親和性の変化に部分的に起因する。
  • 特定の形質因果バリアントとそのメカニズムを特定することは、遺伝学における課題のままである。

研究 の 目的:

  • ヒト形質を因果的に変化させる候補バリアントを特定および提案すること。
  • 転写因子結合の変化に関連する形質変動を調査する方法を開発すること。

主な方法:

  • クロマチン免疫沈降シーケンシングデータを解析するために、計算ツールであるbaal-nfを利用した。
  • 転写因子および補因子結合モチーフ内のヘテロ接合部位で対立遺伝子特異的結合部位を特定した。
  • 機能的バリアントを特定するために親和性一致位置に焦点を当てた。

主要な成果:

  • ヒト形質を因果的に変化させる強力な候補として1,935のバリアントを提案した。
  • 特定された対立遺伝子特異的結合部位が進化的に保存されていることを実証した。
  • ヒト形質および遺伝子発現との関連でこれらの部位の濃縮を示した。

結論:

  • baal-nf法は、高品質の対立遺伝子特異的結合部位を効果的に特定する。
  • これらの発見は、ヒト形質変動の遺伝的基盤を研究するための貴重なリソースを提供する。
  • 転写因子結合の変化は、ヒト形質多様性に寄与する重要なメカニズムである。