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Related Concept Videos

Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
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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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Duplication of Chromatin Structure02:05

Duplication of Chromatin Structure

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The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
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Epigenetic Regulation01:37

Epigenetic Regulation

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Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
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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
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
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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. 
Topologically Associated Domains (TADs)
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Updated: Jul 23, 2025

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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Chromatin structure and context-dependent sequence features control prime editing efficiency.

Somang Kim1,2, Jimmy B Yuan1,2, Wendy S Woods3

  • 1Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL, United States.

Frontiers in Genetics
|July 17, 2023
PubMed
Summary
This summary is machine-generated.

Statistical models identify key features for optimizing prime editing (PE) efficiency. Understanding DNA structure and specific nucleotide sequences in prime editing guide RNA (pegRNA) significantly improves genome editing outcomes.

Keywords:
CRISPR–Cas9DNA-RNA hybridizationheterochromatinmachine learningneural network interpretationnucleosome positioningnucleotide preferenceprime editing

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A Method to Study de novo Formation of Chromatin Domains
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A Method to Study de novo Formation of Chromatin Domains
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Area of Science:

  • Molecular Biology
  • Genomics
  • Bioinformatics

Background:

  • Prime editing (PE) is a versatile CRISPR-Cas9 genome editing technology.
  • Current PE constructs exhibit variable efficiency, necessitating experimental optimization.

Purpose of the Study:

  • Develop statistical models to identify factors influencing PE efficiency.
  • Provide guidelines for designing more effective PE systems.

Main Methods:

  • Statistical modeling to analyze epigenomic and sequence features of target sites.
  • Investigated effects of chromatin structure (heterochromatin, nucleosomes) on editing.
  • Analyzed sequence composition (G/C nucleotides, PAM, template regions) of prime editing guide RNA (pegRNA).

Main Results:

  • Constitutive heterochromatin and nucleosome occlusion hinder PE efficiency.
  • Specific G/C nucleotide positions in pegRNA's primer-binding site (PBS) and reverse transcription (RT) template enhance editing.
  • Identified AGG as a preferred protospacer adjacent motif (PAM) and a guanine four bases downstream of PAM facilitating editing.
  • Discovered multi-nucleotide preferences and base dependencies within pegRNA using neural network analysis.

Conclusions:

  • Epigenomic context and pegRNA sequence features critically impact PE efficiency.
  • Optimized PE designs can be achieved by considering identified sequence and structural determinants.
  • This study clarifies previous findings and offers a predictive framework for enhancing prime editing outcomes.