From Proteopedia
proteopedia linkproteopedia linkHistone H3.3
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Function
histone H3 replaces H3 in a range of nucleosomes in active genes and it takes over the original H3 in non dividing cells. Nucleosomes wrap around and compact DNA into chromatin which limits DNA access to cellular machineries which need DNA as a template. Histones play an important role in regulation of transcription, DNA repair, DNA replication and also chromosomal stability. Access to DNA is regulated by post-translational modifications of histones which is called a histone code, and nucleosome remodeling. It also serves as a replacement histone that's imbedded chromatin regions by the HIRA chaperone, after the depletion of the H3.1 during transcription and DNA repair.
Disease
There have been studies that have identified mutations encoding a K27M substitution and there have also been mutations that encoded
GLY 34 to ARG or VAL called the G34R/V substitution. K27M tumors are present in ex: spinal cord, thalamus, pons, brainstem and G34R/V tumors are shown in the cerebral hemispheres. There are mutations in H3.3 that are found in different types of bone tumors like chrondroblastoma for example and giant cell tumors of the bone. Chondroblastomaarises in children and in young adults in the cartilage of the growth plates of the long bones and is most typically benign.
Relevance
Histone octamer containing two of H2A, H2B, H3 and H4 and the octamer wraps 147bp of DNA. H3.3 interacts with HIRA which is a chaperone and ZMYND11 when trimethylated at
Structural highlights
CENP-Ais a centromere specific variant of Histone H3 and it's controlled in normal cells and its chromosome localization is heavily restricted in the centromere regions. It can be over expressed in cancer cells and also be mislocalized ectopically in the form of heterotypic nucleosomes containing H3.3.
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References
1. Arimura, Y.; Shirayama, K.; Horikoshi, N.; Fujita, R.; Taguchi, H.; Kagawa, W.; Fukagawa, T.; Almouzni, G.; Kurumizaka, H. Crystal structure and stable property of the cancer-associated heterotypic nucleosome containing CENP-A and H3.3. https://www.nature.com/articles/srep07115 (accessed Nov 1, 2020).
2. Cancer Discovery Science Writers. Histone H3.3 Mutations Are Cancer Type-Specific. https://cancerdiscovery.aacrjournals.org/content/3/12/1329.1 (accessed Nov 14, 2020).
3. Gianno, F.; Antonelli, M.; Ferretti2018, E.; Massimino, M.; Arcella, A.; Giangaspero, F. Pediatric high-grade glioma: A heterogeneous group of neoplasms with different molecular drivers. 
(accessed Nov 16, 2020).
4. Kallappagoudar, S.; Yadav, R. K.; Lowe, B. R.; Partridge, J. F. Histone H3 mutations--a special role for H3.3 in tumorigenesis? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446520/ (accessed Nov 1, 2020).
5. Morell, N.; Rajani, R. Chondroblastoma - OrthoInfo - AAOS. https://orthoinfo.aaos.org/en/diseases--conditions/chondroblastoma (accessed Nov 16, 2020).
6. UniProt ConsortiumEuropean Bioinformatics InstituteProtein Information ResourceSIB Swiss Institute of Bioinformatics. Histone H3.3. https://www.uniprot.org/uniprot/P84243 (accessed Nov 1, 2020).
7.Yuen, B. T. K.; Knoepfler, P. S. Histone H3.3 mutations: a variant path to cancer. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882088/ (accessed Nov 16, 2020).
