ミオカルディンおよび三元複合因子は,SRFが滑らかな筋肉の遺伝子発現を制御するために競合する
Zhigao Wang1, Da-Zhi Wang, Dirk Hockemeyer
1Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, Texas 75390-9148, USA.
Nature
|March 12, 2004
まとめ
滑らかな筋肉の細胞は,
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- 遺伝子規制 遺伝子規制
背景:
- 滑らかな筋肉細胞はフェノタイプの可塑性を発揮し,分化状態と増殖状態を切り替える.
- この可塑性を支配する転写メカニズムは完全に理解されていません.
- 血清応答因子 (SRF) は,滑らかな筋肉の遺伝子発現を調節する上で重要な役割を果たします.
研究 の 目的:
- 滑らかな筋肉細胞のフェノタイプの可塑性を制御する転写メカニズムを解明する.
- SRF媒介による遺伝子調節における,ミオカルディンおよび三元複合因子 (TCFs) の役割を調査する.
- 成長信号が滑らかな筋肉の遺伝子発現にどのように影響するかを判断する.
主な方法:
- SRF,ミオカルディン,TCF (特にエルク-1) の相互作用を調査した.
- 成長信号が滑らかな筋肉の遺伝子発現に与える影響を分析した.
- 変異した滑らかな筋肉のプロモーターを使用して,TCF機能を in vivo で評価しました.
主要な成果:
- 成長信号は,エルク-1をSRFからミオカルディンを置換するように誘導し,滑らかな筋肉の遺伝子を抑制します.
- MyocardinとElk-1は,SRFの同じ結合部位を争っている.
- TCFは,胚性心臓における子宮外転写によって示されているように,生体内での滑らかな筋肉の遺伝子発現を抑制するために重要である.
結論:
- 成長と発達のシグナルは,滑らかな筋肉の遺伝子発現を動的に調節する.
- 対抗性共因子 (ミオカルディンとエルク-1) とのSRF関連のバランスは,滑らかな筋肉細胞の現象型を決定する.
- TCFは,滑らかな筋肉の発達と可塑性における重要な肌性抑制剤として作用する.
関連する概念動画
Co-activators and Co-repressors
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...
Master Transcription Regulators
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...
Co-activators and Co-repressors
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...
Master Transcription Regulators
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...
TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Smooth Muscle Contraction
Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...


