Target intelligence / Profile preview

Nucleosome

Molecular classification
Other (It is a structural protein-DNA complex), Histone modification substrate (Nucleosome is the substrate for histone-modifying enzymes), Structural unit of chromatin
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Overview

The Nucleosome is the fundamental structural unit of chromatin in eukaryotic cells. It consists of approximately 147 base pairs of genomic DNA wrapped in a left-handed superhelix around a histone octamer (containing two copies each of histones H2A, H2B, H3, and H4). Linker DNA between nucleosomes may associate with histone H1, forming the chromatosome. The nucleosome provides the first level of DNA compaction, regulates gene accessibility, and acts as a dynamic signaling hub for chromatin-modifying proteins and epigenetic marks. Structural dynamics of nucleosome positioning and histone modifications are essential for controlling gene expression, DNA replication, repair, recombination, and overall genome stability. Aberrations in nucleosome structure or function contribute to cancer and other diseases that involve epigenetic dysregulation. Drugs targeting the nucleosome or associated epigenetic enzymes represent an active area of therapeutic development, although safety concerns remain concerning the non-specific effects on gene expression and chromatin state.

Other names
Nucleosome core particleChromatosome (when including linker histone H1)Histone-DNA complexNCPNucleosome particle
02

Mechanism of action

Epigenetic enzyme modulation: Drugs alter histone post-translational modifications, affecting nucleosome structure and gene expression; Chromatin accessibility alteration: Remodelers and inhibitors can reposition or evict nucleosomes, regulating DNA accessibility; Transcriptional regulation: Changing nucleosome dynamics to up- or down-regulate specific genes

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Biological functions

Genomic DNA packagingGene regulation via chromatin accessibility and structureEpigenetic regulation through histone modifications (methylation, acetylation, phosphorylation, etc.)Scaffold for DNA-templated processes: replication, repair, recombination, transcription
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Disease associations

Cancer (altered nucleosomes and histone modifications play roles in carcinogenesis)Neurodegenerative disease (epigenetic dysfunctions involving nucleosomes can contribute to pathogenesis)Other disorders involving epigenetic and chromatin remodeling aberrations
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Safety considerations

Off-target effects due to broad modulation of chromatin and epigenetic marksGlobal transcriptional dysregulation and toxicityPotential mutagenesis and genomic instability from improper chromatin remodeling
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Interacting drugs

Histone deacetylase inhibitors (HDAC inhibitors; e.g., vorinostat, panobinostat)

4 more in the full profile.

07

Biomarkers

Global histone modification patterns (e.g., H3K27me3, H3K9ac, H4K20me3)Nucleosome occupancy or positioning signaturesCirculating cell-free nucleosome fragments in plasma (experimental/clinical utility in cancer diagnosis and prognosis)

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