MyoDによるc-fosプロモーターの抑制は,筋肉細胞の分化に起因する

D Trouche¹, M Grigoriev, J L Lenormand

¹Laboratoire de Biologie des Tumeurs Humaines, CNRS URA 1156, Villejuif, France.

Nature

|May 6, 1993

まとめ

筋肉細胞の分化には,細胞増殖を阻害するMyoDが含まれています. この研究は,MyoDが成長に関連する遺伝子c-fosをそのプロモーターに結合して抑制し,細胞の成長を抑制することを示しています.

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
遺伝学遺伝学とは

背景:

末端の分化と細胞増殖は,特に筋肉細胞では,しばしば相互排斥的である.
ミオゲネシスは,プロトオンコゲンc-fos.fosのようなミトゲンとオンコゲンによって抑制されます.
MyoDは筋肉特有の転写因子であり,分化を促進し,増殖を阻害する.

研究の目的:

筋肉細胞の分化過程におけるMyoDとc-fos発現の相互作用を調査する.
MyoDが細胞の成長を否定的に調節するメカニズムを解明する.

主な方法:

MyoD誘発の筋肉細胞分化中のc-fos発現の分析.
c-fos プロモーターのMyoD結合部位を特定する.
c-fos遺伝子の血清応答性を阻害するMyoDの役割の実証.

主要な成果:

c-fos発現は,筋肉細胞の分化中に著しく低下し,MyoD活動と相関しています.
c-fosプロモーターの血清反応要素内に機能的なMyoD結合部位が特定されました.
MyoDはc-fosの転写抑制剤として作用し,その血清応答性を抑制します.

結論:

MyoDは,c-fos転写を否定的に調節し,筋肉の分化中に細胞増殖の抑制に貢献します.
この発見は,MyoDが,部分的に,c-fos.fos.のような成長反応性遺伝子の転写不活性化を通じて,その抗増殖効果を媒介することを示唆している.

さらに関連する動画

14:47

Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry

Published on: May 17, 2016

10:22

Studying Muscle Transcriptional Dynamics at Single-molecule Scales in Drosophila

Published on: September 8, 2023

関連する概念動画

02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...

02:04

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...

02:23

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...

01:13

Formation of Muscle Fibers from Myoblasts

De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription factors...

02:23

Master Transcription Regulators

01:29

Somatic to iPS Cell Reprogramming

Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012 for this...

関連する実験動画