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CRISPR-Mediated Reorganization of Chromatin Loop Structure
Published on: September 14, 2018
Chromatin-Remodeling Components of the BAF Complex Facilitate Reprogramming.
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
Summary
Scientists identified the BAF chromatin-remodeling complex as key to increasing somatic cell reprogramming efficiency. This discovery enhances the generation of pluripotent cells, crucial for regenerative medicine.
Area of Science:
- Cellular reprogramming
- Chromatin remodeling
- Stem cell biology
Background:
- Somatic cell reprogramming using Oct4, Sox2, Klf4, and c-Myc factors has low efficiency.
- Understanding factors that enhance reprogramming is critical for advancing regenerative medicine.
Purpose of the Study:
- To identify novel factors that significantly increase somatic cell reprogramming efficiency.
- To elucidate the mechanism by which these factors enhance reprogramming.
Main Methods:
- Developed an assay screening nuclear fractions for Oct4 reactivation.
- Utilized proteomics to identify key proteins involved in reprogramming.
- Validated the role of identified factors in enhancing reprogramming efficiency.
Main Results:
- Identified components of the ATP-dependent BAF chromatin-remodeling complex.
- BAF complex components significantly increased reprogramming efficiency, even without c-Myc.
- Reprogrammed cells demonstrated pluripotency and germline transmission capabilities.
- BAF complex facilitates reprogramming by enhancing Oct4 binding to target promoters.
Conclusions:
- The BAF chromatin-remodeling complex is a critical mediator of efficient somatic cell reprogramming.
- Overexpression of BAF components offers a promising strategy for generating reprogrammed cells with high efficiency.
- This finding advances the potential of using reprogrammed cells for therapeutic applications.
Related Concept Videos
01:32Chromatin 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...
02:54Nucleosome 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...
02:25Spreading 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
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Writers
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01:24Methods 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.
02:32Histone 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
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02:32Histone 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,...