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Related Concept Videos

Nucleosome Remodeling02:54

Nucleosome Remodeling

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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...
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Histone Modification02:32

Histone Modification

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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.
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The Nucleosome01:19

The Nucleosome

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Human DNA is almost two meters long. However, it is compressed inside a tiny nucleus measuring only a few microns in diameter. To make this degree of compaction possible, DNA is organized into several sequential levels so that it can fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
In a chromosome, DNA is wound twice around a protein complex called a histone octamer core, which consists of 8 histone proteins. This...
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The Nucleosome02:33

The Nucleosome

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DNA in a human cell is almost 2m long and it is packed inside a tiny nucleus that is only a few microns in diameter. The level of compaction of DNA inside the nucleus is astonishing. It is organized into several sequentially higher levels of compaction to fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...
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The Nucleosome Core Particle02:10

The Nucleosome Core Particle

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Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
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The Nucleosome Core Particle01:12

The Nucleosome Core Particle

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Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
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Author Spotlight: Efficient Nucleosome Reconstitution for Single-Molecule Techniques
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Author Spotlight: Efficient Nucleosome Reconstitution for Single-Molecule Techniques

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Single-molecule decoding of combinatorially modified nucleosomes.

Efrat Shema1, Daniel Jones2, Noam Shoresh3

  • 1Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Science (New York, N.Y.)
|May 7, 2016
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Summary
This summary is machine-generated.

New single-molecule imaging decodes histone modifications on nucleosomes, revealing distinct states linked to cell potency and epigenetic regulation. This technology advances chromatin biology research.

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The ChroP Approach Combines ChIP and Mass Spectrometry to Dissect Locus-specific Proteomic Landscapes of Chromatin
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Area of Science:

  • Chromatin biology
  • Epigenetics
  • Molecular imaging

Background:

  • Combinations of histone modifications regulate gene expression but are difficult to study with current technologies.
  • Understanding these combinatorial states is crucial for deciphering epigenetic regulation and cell differentiation.

Purpose of the Study:

  • To develop and apply a high-throughput single-molecule imaging technology to decode combinatorial histone modifications on individual nucleosomes.
  • To investigate how these modification states vary between pluripotent and lineage-committed cells.
  • To assess the impact of genetic and chemical perturbations on specific nucleosome modification states.

Main Methods:

  • High-throughput single-molecule imaging of nucleosomes.
  • Analysis of millions of individual nucleosomes from stem cells and differentiated cells.
  • Integration of proteomic analysis with single-molecule DNA sequencing.

Main Results:

  • Identification of bivalent nucleosomes (repressive and activating marks) and other combinatorial states.
  • Demonstration that the prevalence of these states correlates with developmental potency.
  • Evidence that chromatin enzyme perturbations specifically impact nucleosomes with defined modification states.

Conclusions:

  • The developed single-molecule imaging platform effectively decodes combinatorial histone modifications.
  • This technology provides novel insights into epigenetic regulation and chromatin dynamics during cell development.
  • The platform holds significant potential for addressing fundamental questions in chromatin biology.