hTERTプロモーターにおける2つの異なるG-四重複形状の共存
Kah Wai Lim1, Laurent Lacroix, Doris Jia En Yue
1School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
Journal of the American Chemical Society
|August 14, 2010
まとめ
ヒトテロメラーゼ (hTERT) プロモーターは,がん細胞の生存に不可欠なG四重複構造を形成する. この研究は,均衡状態にある2つの異なるG-四重複形状を明らかにし,その調節に関する洞察を提供します.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 構造生物学 構造生物学とは
背景:
- 人間のテロメラーゼ (hTERT) 遺伝子は,がん細胞の増殖に極めて重要です.
- hTERTプロモーターには,G-四重複構造を形成する傾向のあるG-豊富な配列が含まれています.
- G四重複体は,遺伝子調節における潜在的な役割を持つ非正規のDNA二次構造である.
研究 の 目的:
- hTERTプロモーターにおける特定のG豊富な配列のG四重複形成ポテンシャルを調査する.
- このシーケンスによって採用された異なるG-四重複形状の構造特性を解明する.
- これらの形状の間の均衡を左右する要因を理解する.
主な方法:
- 溶液構造の決定のための核磁気共鳴 (NMR) スペクトロスコーピー.
- 形状の変化を研究するための円形の二重化 (CD) スペクトロスコーピー.
- サイト・ディレクテッド・ミュータゲネシスと,構造的安定性を探求するための様々な実験条件.
主要な成果:
- hTERTプロモーターからの特定のG豊富な配列は,カリウム溶液で2つの異なるG四重複構造を形成する: (3+1) と並列鎖のG四重複.
- 詳細なNMR構造は,G-テトラドコア,特定のループ構造,および両方の形状のA.T塩基ペアをカバーするなどの保存された元素を明らかにします.
- NMRとCDのデータは,実験的な変異とともに,これらの2つの構造の共存と均衡を証明しています.
結論:
- hTERTプロモーターのG-四重複配列は,複数の安定した形状を採用することができます.
- G-テトラドのコアアレンジメントとループ構造を含む構造的特徴は,特定の形状の好みを左右します.
- これらのG-四重複のダイナミクスを理解することは,hTERTの調節とがんにおける潜在的な治療標的化におけるそれらの役割を探求するために不可欠です.
関連する概念動画
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...
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...
The Eukaryotic Promoter Region
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...
The Eukaryotic Promoter Region
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...
Bacterial Transcription
RNA polymerase (RNAP) carries out DNA-dependent RNA synthesis in both bacteria and eukaryotes. Bacteria do not have a membrane-bound nucleus. So, transcription and translation occur simultaneously, on the same DNA template.
Transcription can be divided into three main stages, each involving distinct DNA sequences to guide the polymerase. These are:
Transcription can be divided into three main stages, each involving distinct DNA sequences to guide the polymerase. These are:
Transcription Attenuation in Prokaryotes
Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
There are several different mechanisms used to attenuate transcription. In ribosome mediated...


