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Spreading of Chromatin Modifications02:25

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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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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.
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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 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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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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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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RNA-modifying enzymes and their function in a chromatin context.

Konstantinos Tzelepis1, Oliver Rausch2, Tony Kouzarides3

  • 1The Gurdon Institute and Department of Pathology, University of Cambridge, Cambridge, UK.

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|October 5, 2019
PubMed
Summary

Specific RNA modifications are linked to chromatin, influencing gene regulation during transcription. This review explores their roles in health and disease, and therapeutic potential.

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Gene Regulation

Background:

  • RNA modifications are increasingly recognized for their roles beyond translation.
  • Emerging evidence links RNA modifications to chromatin structure and function.
  • These modifications play a crucial role in co-transcriptional processes.

Purpose of the Study:

  • To review the co-transcriptional roles of RNA modifications.
  • To discuss their influence in normal physiology and disease states.
  • To explore the translational potential of targeting RNA-modifying enzymes.

Main Methods:

  • Literature review of recent research on RNA modifications and chromatin.
  • Analysis of studies investigating RNA modification deposition and function during transcription.
  • Discussion of novel technical approaches and their therapeutic implications.

Main Results:

  • Specific RNA modifications are deposited co-transcriptionally.
  • These modifications directly influence chromatin organization and gene regulation.
  • Dysregulation of RNA modifications is implicated in various diseases.

Conclusions:

  • RNA modifications are integral to co-transcriptional gene regulation.
  • Targeting RNA-modifying enzymes offers promising therapeutic strategies for diseases.
  • Advancements in technology will enhance the study and application of RNA modifications.