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Related Concept Videos

Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

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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...
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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.
Acetylation
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Histone Modification02:32

Histone Modification

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Chromatin Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

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Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
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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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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
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Updated: Dec 13, 2025

Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
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Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark

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Histone methyltransferase activity programs nuclear peripheral genome positioning.

Kelvin See1, Anna A Kiseleva1, Cheryl L Smith1

  • 1Department of Medicine and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Developmental Biology
|July 27, 2020
PubMed
Summary
This summary is machine-generated.

Researchers developed a CRISPR-based system to visualize and relocate genomic loci in live cells. This system uses epigenetic modifications to tether DNA regions to the nuclear periphery, aiding in understanding genome organization.

Keywords:
Cas9 CRISPRChromatin organizationH3K9me2HMTsNuclear periphery

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Area of Science:

  • * Molecular Biology
  • * Epigenetics
  • * Cell Biology

Background:

  • * The spatial arrangement of the genome within the nucleus is crucial for cellular functions like development and gene regulation.
  • * Genomic regions at the nuclear periphery are associated with specific epigenetic marks (H3K9me2), and their repositioning is linked to cell differentiation.
  • * Understanding dynamic chromatin organization is key to deciphering gene expression control.

Purpose of the Study:

  • * To develop a novel CRISPR-based system for visualizing and manipulating genomic locus positions in live cells.
  • * To investigate the role of epigenetic modifications, specifically H3K9me2, in tethering genomic regions to the nuclear periphery.
  • * To provide a tool for studying the functional impact of forced chromatin relocalization.

Main Methods:

  • * Development of a CRISPR-Cas9 system for targeted genomic locus manipulation.
  • * Utilizing fusion proteins: dCas9-Lap2β for direct tethering and dCas9 fused to G9a (a histone methyltransferase) for epigenetic modification.
  • * Live-cell imaging to track genomic locus movement and localization patterns.

Main Results:

  • * Successfully demonstrated forced spatial relocalization of a target genomic locus to the nuclear periphery using the developed CRISPR system.
  • * Showed that tethering can be achieved either by direct binding to the nuclear membrane via dCas9-Lap2β or by inducing H3K9me2 marks via dCas9-G9a.
  • * Confirmed that the enzymatic activity of G9a is essential for H3K9me2-mediated localization and that this process is independent of nuclear actin polymerization.

Conclusions:

  • * Epigenetic histone modifying enzymes play a significant role in the spatial organization of chromatin.
  • * The developed CRISPR-based system enables effective tracking and manipulation of targeted genomic regions in live cells.
  • * This technology offers new avenues for exploring the functional consequences of genome spatial organization.