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Description

Histone H3.3 (UniProt: P84243, also known as H3.3) is encoded by the H3F3A (also known as H3.3A, H3F3, PP781, H3F3B, H3.3B) gene (Gene ID: 3020, 3021) in human. Histone H3.3 is a highly conserved variant form of Histone H3, which replaces conventional H3 in a wide range of nucleosomes in active genes. Histone H3 has two main variants, H3.1 and H3.3, which show different genomic localization patterns in animals. The H3.1 and H3.3 complexes also possess distinct histone chaperones, CAF-1 and HIRA, which play important role in mediating DNA-synthesis-dependent and -independent nucleosome assembly. Histone H3.1 serves as the canonical histone, which is incorporated during DNA replication, whereas H3.3 acts as the replacement histone that can be incorporated outside of S-phase during chromatin-disrupting processes like transcription. Histone H 3.3 constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. It is associated with actively expressed genes in both animals and plants. It is predominantly enriched near transcription end sites (TES) of genes and positively associated with transcription. Histone H3 contains a main globular domain and a long N-terminal tail and is involved with the structure of the nucleosomes of the 'beads on a string' structure. The N-terminal tail of histone H3 protrudes from the globular nucleosome core and can undergo several different types of epigenetic modifications that influence cellular processes. These modifications include the covalent attachment of methyl or acetyl groups to lysine and arginine amino acids and the phosphorylation of serine or threonine. Mutations in Histone H3.3 have been implicated in a high proportion of malignant pediatric brain cancers. K4M mutation is reported to inhibit H3K4 methylation and prevent enhancer activation in adipogenesis by destabilizing MLL4/MLL4 proteins, but does not affect MLL1, MLL2, SETA1, or SET1B. Expression of K4M in lineage-specific precursor cells is shown to deplete H3K4 methylation and impair adipose tissue and muscle development. (Ref.: Jang, Y., et al. (2019). Nucleic Acids Res. 47(2), 607-620, Tagami, H., et al. (2004). Cell, 116(1), 51-61).