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Related Concept Videos

Nucleosome Remodeling02:54

Nucleosome Remodeling

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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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Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
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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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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 nucleoid represents a structurally and functionally distinct region within prokaryotic cells, where the cell's DNA and associated proteins are housed. Unlike eukaryotic cells, prokaryotes lack a membrane-bound nucleus, and the nucleoid facilitates the organization and accessibility of the genetic material within this constraint. The DNA in most bacteria and archaea exists as a single, circular, double-stranded molecule that is highly compacted through supercoiling and interactions with...
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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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Updated: Aug 26, 2025

Biochemical Assays for Analyzing Activities of ATP-dependent Chromatin Remodeling Enzymes
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Origin recognition complex harbors an intrinsic nucleosome remodeling activity.

Sai Li1, Michael R Wasserman1, Olga Yurieva2

  • 1Laboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, NY 10065.

Proceedings of the National Academy of Sciences of the United States of America
|October 10, 2022
PubMed
Summary

The origin recognition complex (ORC) remodels chromatin by ejecting specific histone dimers from nucleosomes, ensuring DNA replication origins are accessible. This ATP-dependent process is crucial for efficient origin licensing and activity.

Keywords:
DNA replicationnucleosomenucleosome remodelingorigin of replicationorigin recognition complex

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Area of Science:

  • Molecular Biology
  • Chromatin Biology
  • DNA Replication

Background:

  • Eukaryotic DNA replication initiates at origins recognized by the origin recognition complex (ORC).
  • Nucleosomes can impede ORC binding and MCM helicase loading at replication origins.
  • Autonomously replicating sequences (ARSs) are largely nucleosome-depleted but can still be inhibited.

Purpose of the Study:

  • To investigate the mechanism by which ORC interacts with and potentially remodels nucleosomes at replication origins.
  • To determine if ORC can overcome nucleosome-mediated inhibition of origin licensing.

Main Methods:

  • Single-molecule visualization techniques using purified proteins.
  • Biochemical assays to study histone eviction and DNA binding.

Main Results:

  • ORC actively ejects histone H2A-H2B dimers from nucleosomes in an ATP-dependent manner.
  • ORC preferentially evicts canonical H2A over the H2A.Z variant.
  • The Orc1 subunit's bromo-adjacent homology (BAH) domain is essential for histone eviction.

Conclusions:

  • ORC functions as a nucleosome remodeler, facilitating origin accessibility.
  • Histone eviction by ORC is a key step in licensing DNA replication origins.
  • The findings reveal a novel role for ORC in chromatin regulation during DNA replication.