関連する実験動画

Updated: Sep 24, 2025

Assays for Validating Histone Acetyltransferase Inhibitors

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

ヒストンアセチルトランスフェラーゼp300とCBPは,血管の滑らかな筋肉の可塑性における異なる染色体改造プログラムを調整する

Raja Chakraborty^1,2, Allison C Ostriker^1,2, Yi Xie^1,2

¹Departments of Medicine (Cardiovascular Medicine) (R.C., A.C.O., Y.X., J.M.D., P.C., Y.A., J.V., D.M.G., J.H., K.A.M), Yale University School of Medicine, New Haven, CT.

|May 3, 2022

まとめ

ヒストンアセチルトランスファーゼp300とCREB結合タンパク質 (CBP) は,血管性滑らかな筋肉細胞 (VSMC) のフェノタイプにおいて対極的な役割を果たしている. p300やCBPをターゲットにすることで心血管疾患の新たな治療法が提供されるかもしれません

科学分野:

心血管生物学
エピジェネティクス
細胞制御

背景:

血管滑らかな筋肉細胞 (VSMC) のフェノタイプスイッチングは,心血管疾患に関与しています.
TET2のようなエピジェネティック・レギュレータは,VSMCの表型を制御する上で重要な役割を果たします.
同型ヒストンアセチルトランスファーゼp300とCREB結合タンパク質 (CBP) がVSMCの調節における役割は,以前は知られていなかった.

研究の目的:

VSMCのフェノタイプスイッチングにおけるp300とCBPの異なる役割を調査する.
VSMCの規制におけるp300とCBPの機能の基礎となる分子メカニズムを解明する.
心血管疾患モデルにおけるp300またはCBPを標的とする治療の可能性を評価する.

主な方法:

ヒトのVSMCでノックダウンを用いてp300とCBPの役割を評価した.
p300とCBPのために誘導性滑らかな筋肉特異ノックアウトマウス (iKO) を利用した.
ヒトの内臓増殖と心臓移植の血管病のサンプルを分析した.

主要な成果:

p300とCBPは逆の機能を示し,p300は収縮性タンパク質を促進し,移動を阻害し,CBPは移動を強化し,収縮性遺伝子を阻害した.
p300 iKOマウスは重度の内臓増殖を示したが,CBP iKOマウスは保護された.
p300はTET2と相互作用してヒストンのアセチル化とDNAのヒドロキシメチル化を調節し,CBPはヒストンの脱エチラゼ (HDAC) を誘導し,TET2の発現を抑制する.

結論:

p300とCBPは,VSMCのフェノタイプ調節において非冗長で対極的な機能を持っています.
これらのヒストンアセチルトランスフェラーゼは,TET2とHDACとの異なる相互作用によって染色体の変化を調整する.
特定のヒストンアセチルトランスフェラーゼを標的とした治療は,心臓血管疾患の潜在的治療戦略です.

キーワード:

アセチル化クロマチンの改造エピジェネティクスヒストンアセチルトランスフェラーゼハイパープラジア滑らかな筋肉細胞

さらに関連する動画

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro

Published on: February 15, 2022

関連する概念動画

Chromatin Modification in iPS Cells

Chromatin Modification in iPS Cells

Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...

Master Transcription Regulators

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...

Spreading of Chromatin Modifications

Spreading of Chromatin Modifications

The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...

Histone Modification

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...

Regulation of Angiogenesis and Blood Supply

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...

Co-activators and Co-repressors

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...