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Target intelligence / Profile preview
Histone H3.3 (H3.3)
- Target
- H3.3
- Molecular classification
- Histone, Chromatin protein, DNA-binding protein, Epigenetic regulator
01
Overview
Histone H3.3 is a replication-independent histone variant encoded by the genes H3F3A and H3F3B. Unlike canonical histones (H3.1 and H3.2), H3.3 is expressed and incorporated into chromatin throughout the cell cycle, independent of DNA replication. It differs from canonical H3 at only a few key amino acids, which enable it to be specifically recognized and deposited into chromatin by dedicated histone chaperones such as HIRA and DAXX. H3.3 is mainly associated with active regions of the genome, and plays critical roles in regulating gene expression, chromatin dynamics, and epigenetic memory. Mutations in H3.3, especially at residues K27 and G34, are recurrent in several aggressive pediatric brain tumors and bone cancers, serving as diagnostic biomarkers and shedding light on the role of chromatin dysregulation in cancer[1][2][3][4][5].
- Other names
- H3-3AH3F3AH3F3BH3.3AH3.3Bhistone H3.3H3 histone family member 3ABRYLIB1PP781H3-3B
02
Mechanism of action
As a structural chromatin protein, H3.3 is not directly targeted by drugs; epigenetic drugs act on enzymes that modify histones, not on H3.3 itself.
03
Biological functions
Chromatin organizationRegulation of gene expressionEpigenetic regulationDNA packagingTranscriptional regulationCell cycle regulationGenome stability
04
Disease associations
CancerNeurodevelopmental diseasesOther (mutations associated with various pediatric tumors and chromatin disorders)
05
Safety considerations
Not directly targeted by therapeutics; safety concerns relate to non-specific targeting of chromatin-modifying enzymes, which can affect global chromatin and gene expression[2][4][5].
06
Biomarkers
H3.3 K27M mutation (biomarker in pediatric gliomas and certain sarcomas)H3.3 G34R/V mutations (biomarkers in specific glioblastoma subtypes)
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