ミトコンドリアDNA配列認識とプロモーター特異的転写抑制のための合成リガンドの作成
Takuya Hidaka1, Ganesh N Pandian2, Junichi Taniguchi1
1Department of Chemistry, Graduate School of Science, Kyoto University , Sakyo, Kyoto 606-8502, Japan.
Journal of the American Chemical Society
|June 15, 2017
まとめ
研究者は,特定のミトコンドリアDNA配列を標的とする新しい合成リガンド,MITO-PIPを開発しました. これらのリガンドはミトコンドリアの遺伝子転写を調節し,ミトコンドリアの疾患に対する潜在的な治療戦略を提供します.
科学分野:
- 生物化学
- 分子生物学
- 遺伝学
背景:
- ミトコンドリアDNA (mtDNA) 変異は様々なヒトの病気と関連しています.
- ミトコンドリアの遺伝子転写の標的型調節は,治療的介入において極めて重要です.
- 既存の合成リガンドには特異性やミトコンドリアを標的とする能力がない.
研究 の 目的:
- ミトコンドリア特有の新合成リガンド (MITO-PIP) の設計と合成.
- MITO-PIPの特定のmtDNA配列を認識し,ミトコンドリア内で局所化する能力を評価する.
- ミトコンドリアの遺伝子転写を調節するMITO-PIPの可能性を評価する.
主な方法:
- ミトコンドリアに浸透するペプチドとピロールイミダゾールポリアミド (PIP) の結合.
- ミトコンドリアの標的化を確認するために,HeLa細胞での細胞局所化研究.
- 配列特異的認識を評価するためのDNA結合測定法
- ミトコンドリア転写因子A (TFAM) の結合抑制と転写抑制の分析
主要な成果:
- MITO-PIPはミトコンドリア内の特定の局所化を示した.
- 配列特異的な方法で標的DNA配列を認識した.
- MITO- PIPは,LSPへのTFAM結合を成功裏に抑制しました.
- MITO- PIPによって標的化された転写抑制が達成された.
結論:
- MITO-PIPはミトコンドリア特有の新種の合成リガンドである.
- これらのリガンドは,mtDNA配列を特異的に標的にし,結合することができる.
- MITO-PIPは,ミトコンドリアの遺伝子転写を調節し,潜在的にmtDNA変異に対処するための調整可能なプラットフォームを提供します.
さらに関連する動画
関連する概念動画
02:13Cooperative Binding of Transcription Regulators
7.4K
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...
7.4K
02:04Co-activators and Co-repressors
8.7K
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...
8.7K
02:53Conservative Site-specific Recombination and Phase Variation
7.0K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
7.0K
02:02Cis-regulatory Sequences
12.0K
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...
12.0K
01:52Eukaryotic Transcription Inhibitors
11.2K
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...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.2K