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Related Concept Videos

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.
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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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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.
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Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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Author Spotlight: An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations
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Predicting active enhancers with DNA methylation and histone modification.

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|November 3, 2023
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We developed a novel method to reduce noise in enhancer RNA (eRNA) detection and created accurate eRNA prediction models using multi-omics data, improving gene regulation studies.

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Area of Science:

  • Molecular Biology
  • Genomics
  • Epigenetics

Background:

  • Enhancers are critical for gene regulation, producing enhancer RNAs (eRNAs).
  • Current eRNA detection methods like CAGE-seq suffer from noise due to eRNA instability.
  • Limited research exists on CAGE-seq noise and eRNA prediction models.

Purpose of the Study:

  • To reduce false positives in eRNA identification.
  • To develop robust eRNA prediction models.
  • To address the challenge of noise in eRNA detection.

Main Methods:

  • Adjusting the statistical distribution of expression levels to minimize noise.
  • Developing prediction models integrating gene expression, DNA methylation, and histone modification data.
  • Validating model performance using intra-cell and cross-cell prediction.

Main Results:

  • A novel method effectively reduced noise in eRNA detection.
  • Developed eRNA prediction models achieved high accuracy (AUC ~0.95 intra-cell, ~0.9 cross-cell).
  • The models demonstrated robustness across different cellular contexts.

Conclusions:

  • The proposed method successfully attenuates noise from stochastic RNA production.
  • The eRNA prediction model shows significant accuracy and robustness.
  • This work provides a valuable tool for accurate eRNA detection and prediction.