血液形成にはコアクティベーターp300の転写因子結合表面が必要である
Lawryn H Kasper1, Fayçal Boussouar, Paul A Ney
1Department of Biochemistry, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee 38105, USA.
Nature
|October 18, 2002
まとめ
コアクティベーターCBPとp300のKIXドメインは,マウスの発達において異なる役割を果たしています. p300のKIXドメインを破壊すると,血液細胞の形成が損なわれ,CBPのKIXドメインの変異は最小限の影響を及ぼします.
科学分野:
- 分子生物学は分子生物学である.
- 発達生物学 発達生物学について
- 遺伝学 遺伝学とは
背景:
- CBP (CREB結合タンパク質) とp300は,遺伝子調節に関与する重要な共同活性化剤である.
- これらのタンパク質は,正常な発達に不可欠なアダプター分子とタンパク質アセチルトランスフェラーゼ機能を備えています.
- CBPとp300の変異は,血液形成性および上皮性腫瘍を含む様々な癌と関連しています.
研究 の 目的:
- CBPとp300のコアクティベーターのインビボ機能を調査する.
- 哺乳類の発達におけるCBPとp300のKIXドメインの重要な役割を決定する.
- 血液形成の調節におけるCBPとp300 KIXドメインの特定の機能を明らかにする.
主な方法:
- CBPとp300のKIXドメインの標的点変異を持つマウスの生成.
- ミュータントマウスにおける血液形成の発達と多系系欠陥の分析.
- c-Mybとp300 KIXドメインの突然変異を含む遺伝子相互作用の研究.
主要な成果:
- p300 KIXドメインが破壊されたマウスは,貧血とB細胞欠乏症を含む重度の多系血球形成の欠陥を示します.
- CBP KIXドメインの変異は,マウスの大きな発達異常を引き起こさない.
- c-Mybとp300 KIXドメイン変異の間のシネギスティック遺伝的相互作用は,メガカリオサイト発達のp300へのc-Myb結合の重要な役割を強調しています.
結論:
- CBPとp300のKIXドメインは,体内で,特に血液形成において,非冗長かつ対照的な機能を有する.
- 転写因子c-Mybがp300 KIXドメインに結合することは,メガカリオサイトの発達と機能に極めて重要です.
- これらの発見は,複雑な生物学的プロセスを調節する高度に関連したコアクティベーターの特殊な役割を明らかにしています.
関連する概念動画
02:16Transcription 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...
02:16Transcription 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...
02:04Co-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...
02:42Eukaryotic Transcription Activators
Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...
01:30General 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...
02:04Co-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...