BAF複合体のクロマチン再構成構成要素は,再プログラミングを容易にする

Nishant Singhal¹, Johannes Graumann, Guangming Wu

¹Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, D-48149 Münster, Germany.

Cell

|June 17, 2010

まとめ

科学者は,体細胞の再プログラム効率を高めるための鍵としてBAF染色体再構成複合体を特定しました. この発見は,再生医療にとって極めて重要な,多能細胞の生成を促進します.

科学分野:

細胞を再プログラムする.
クロマチンの改造
幹細胞生物学幹細胞生物学とは

背景:

Oct4,Sox2,Klf4,c-Myc因子を用いた体細胞再プログラミングは効率が低い.
再プログラムを促進する要因を理解することは,再生医療の進歩に不可欠です.

研究の目的:

ソマティック細胞の再プログラム効率を大幅に高める新しい要因を特定する.
これらの要因が再プログラミングを強化するメカニズムを解明する.

主な方法:

Oct4再活性化のための核分子をスクリーニングするアッセイを開発した.
プロテオミクスを活用して,再プログラムに関与する重要なタンパク質を特定しました.
再プログラム効率の向上における,特定された要因の役割を検証した.

主要な成果:

ATPに依存するBAF染色体改造複合体の特定された成分.
BAFの複合コンポーネントは,c-Myc.なしででも,再プログラミング効率を大幅に高めました.
再プログラムされた細胞は,多能性と生殖系統の伝播能力を示した.
BAF複合体は,ターゲットプロモーターへのOct4結合を強化することにより,再プログラミングを容易にする.

結論:

BAF染色体再構成複合体は,効率的な体細胞再プログラミングの重要な媒介体である.
BAFコンポーネントの過剰発現は,高効率で再プログラムされた細胞を生成するための有望な戦略を提供します.
この発見は,再プログラムされた細胞を治療用途で使用する可能性を高めています.

さらに関連する動画

10:28

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

08:44

Generation and Purification of Human INO80 Chromatin Remodeling Complexes and Subcomplexes

Published on: October 23, 2014

関連する概念動画

01:32

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...

02:54

Nucleosome Remodeling

Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...

02:25

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 is an enzyme that can...

01:24

Methods of Nuclear Reprogramming

Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for injury repair.

02:32

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 deacetylase,...