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CRISPR-Mediated Reorganization of Chromatin Loop Structure
Published on: September 14, 2018
BAF复合体的染色体重塑组件有助于重编程
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
概括
科学家们确定BAF染色体重塑复合体是提高体细胞重编程效率的关键. 这一发现增强了多能细胞的产生,这对再生医学至关重要.
科学领域:
- 细胞重新编程的细胞重编程.
- 染色体重塑 染色体重塑 的方法
- 干细胞生物学 干细胞生物学
背景情况:
- 使用Oct4,Sox2,Klf4和c-Myc因子进行体细胞重编程的效率很低.
- 了解增强重编程的因素对于推进再生医学至关重要.
研究的目的:
- 确定显著提高体细胞重编程效率的新型因素.
- 阐明这些因素增强重新编程的机制.
主要方法:
- 开发了一种分析选核分数Oct4重新激活的测试方法.
- 利用蛋白质组学来识别参与重编程的关键蛋白质.
- 验证了确定因素在提高重新编程效率方面的作用.
主要成果:
- 鉴定了依赖ATP的BAF染色体重塑复合物的组成部分.
- BAF复杂组件显著提高了重编程效率,即使没有c-Myc.
- 重编程的细胞表现出多能性和生殖系传播能力.
- BAF复合物通过增强Oct4对目标促进者的结合来促进重新编程.
结论:
- BAF染色体重塑复合体是有效的体细胞重编程的关键媒介.
- 过度表达BAF组件为产生高效率的重编程细胞提供了一个有希望的策略.
- 这一发现提升了用于治疗应用的重编程细胞的潜力.
相关概念视频
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...
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...
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...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
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...
Writers
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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.
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,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
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,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...

