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The Nucleosome02:33

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DNA in a human cell is almost 2m long and it is packed inside a tiny nucleus that is only a few microns in diameter. The level of compaction of DNA inside the nucleus is astonishing. It is organized into several sequentially higher levels of compaction to fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
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Human DNA is almost two meters long. However, it is compressed inside a tiny nucleus measuring only a few microns in diameter. To make this degree of compaction possible, DNA is organized into several sequential levels so that it can fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
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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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Assembly of Nucleosomal Arrays from Recombinant Core Histones and Nucleosome Positioning DNA
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Inter-nucleosomal communication between histone modifications for nucleosome phasing.

Weizhong Chen1, Yi Liu1,2, Shanshan Zhu1

  • 1Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Plos Computational Biology
|September 7, 2018
PubMed
Summary

Epigenetic modifications on neighboring nucleosomes communicate to regulate gene transcription. A novel interaction between H2A.Z and H4K20me1 establishes nucleosome-free regions and phasing near transcription start sites.

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Area of Science:

  • Epigenetics and Molecular Biology
  • Genomics and Computational Biology

Background:

  • The
  • histone code
  • hypothesis suggests combinatorial epigenetic modifications regulate transcription.
  • Mechanisms of inter-nucleosomal communication and formation of nucleosome patterns remain unclear.

Purpose of the Study:

  • Investigate inter-nucleosomal communication among histone modifications.
  • Determine the functional roles of these interactions in gene regulation and chromatin organization.
  • Elucidate the formation of nucleosome phasing and depletion patterns.

Main Methods:

  • Developed a dynamic Bayesian network (DBN) model to analyze interactions between histone modifications on neighboring nucleosomes.
  • Applied the model to genomic data to identify significant inter-nucleosomal interactions.

Main Results:

  • Confirmed robust inter-nucleosomal interactions near transcription start sites (TSS), transcription termination sites (TTS), and CTCF binding sites, often linked to transcription regulation.
  • Discovered a novel interaction between H2A.Z and H4K20me1 on adjacent nucleosomes, crucial for establishing and maintaining nucleosome-free regions (NFR) and nucleosome phasing.
  • Demonstrated a strong negative correlation between H2A.Z and H4K20me1 levels and the size of NFR and strength of nucleosome phasing around TSS.

Conclusions:

  • Inter-nucleosomal communication is a key mechanism for epigenetic signal propagation and chromatin remodeling.
  • These interactions play significant roles in regulating transcription.
  • The H2A.Z/H4K20me1 interaction provides specific insights into nucleosome organization at regulatory regions.