5つの脊椎動物のCHIP-seqは,転写因子結合の進化のダイナミクスを明らかにしています
Dominic Schmidt1, Michael D Wilson, Benoit Ballester
1Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
まとめ
遺伝子調節は急速に進化しており,ほとんどの転写因子結合部位は種によって異なる. 保存されたDNAの好みにもかかわらず,TF結合の分岐はモチーフ配列の変化によって引き起こされ,規制の進化の洞察を提供します.
科学分野:
- 進化生物学の進化生物学について
- 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.
背景:
- 転写因子 (TF) は,遺伝子発現の重要な調節因子である.
- 遺伝子調節の進化を理解することは,種多様性の解読の鍵です.
研究 の 目的:
- 脊椎動物の肝臓における2つの重要なTFのゲノム全体の結合パターンを調査する.
- 種間のTF結合部位の進化動態と保存を調査する.
主な方法:
- 高通量シーケンシング (ChIP-seq) によるクロマチンの免疫プレシピテーションが採用されました.
- 全ゲノムTF占有率は,CCAAT/エンハンサー結合タンパク質αと肝細胞核因子4αを5種の脊椎動物でマッピングした.
- 分析は,保存された対種固有の結合イベントと,DNA配列の制約との関係に焦点を当てました.
主要な成果:
- TF DNAの結合傾向は保たれていても,ほとんどの結合イベントは種特有である.
- 希少なアライナード・バインディング・イベントは,5つの種すべてで観察されました.
- Binding divergenceは主にTFのバインディングモチーフのシーケンス変化に起因する.
- 失われた結合イベントは,近くで復元されることはめったになく,わずか半分が10 kilobases 内に復元されます.
結論:
- トランスクリプションの調節において,種間の有意な変動が存在します.
- 規制の進化は,動的なTF結合パターンによって特徴付けられています.
- モチーフの配列の変化は,種間の結合分岐の主要な要因である.
関連する概念動画
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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 dimers that...
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...
General 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...
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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...


