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Related Experiment Video

Updated: May 13, 2025

Chromatin Extraction from Frozen Chimeric Liver Tissue for Chromatin Immunoprecipitation Analysis
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Chromatin Extraction from Frozen Chimeric Liver Tissue for Chromatin Immunoprecipitation Analysis

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Predicting gene expression changes from chromatin structure modification.

Swayamshree Senapati1, Inayat Ullah Irshad2, Ajeet K Sharma2,3

  • 1School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Argul, Odisha, 752050, India.

NPJ Systems Biology and Applications
|April 15, 2025
PubMed
Summary
This summary is machine-generated.

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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.
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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.
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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 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 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.
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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.
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This study introduces a computational framework linking chromosome 3D organization (Hi-C) to gene transcription. The model accurately predicts gene expression changes after disrupting a boundary, highlighting the impact of 3D genome structure on gene regulation.

Area of Science:

  • Genomics
  • Computational Biology
  • Molecular Biology

Background:

  • The spatial organization of chromatin is crucial for gene transcription.
  • Connecting population-averaged Hi-C data to functional gene expression outcomes is challenging.

Purpose of the Study:

  • To develop a computational framework linking Hi-C contact maps to gene transcription.
  • To simulate the impact of chromatin structure perturbations on gene expression.

Main Methods:

  • Utilized a bead-spring polymer model informed by Hi-C data to generate 3D chromatin conformations.
  • Employed a Markov chain model coupled with molecular dynamics simulations to link conformations to transcription levels.
  • Simulated the perturbation of a CTCF-mediated TAD boundary.

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Related Experiment Videos

Last Updated: May 13, 2025

Chromatin Extraction from Frozen Chimeric Liver Tissue for Chromatin Immunoprecipitation Analysis
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Chromatin Extraction from Frozen Chimeric Liver Tissue for Chromatin Immunoprecipitation Analysis

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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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Main Results:

  • The framework quantitatively reproduced experimentally observed gene expression changes (sox9 and kcnj2).
  • Demonstrated that disruption of a TAD boundary increased kcnj2 transcription by enhancing enhancer accessibility.
  • The model can identify functional enhancers based on their impact on gene expression.

Conclusions:

  • The developed framework enhances understanding of the relationship between chromosome 3D architecture and gene regulation.
  • This approach provides a quantitative method to assess the functional impact of chromatin spatial organization.