title: Histone H3.3 and cancer: A potential reader connection.
abstract: The building block of chromatin is nucleosome, which consists of 146 base pairs of DNA wrapped around a histone octamer composed of two copies of histone H2A, H2B, H3, and H4. Significantly, the somatic missense mutations of the histone H3 variant, H3.3, are associated with childhood and young-adult tumors, such as pediatric high-grade astrocytomas, as well as chondroblastoma and giant-cell tumors of the bone. The mechanisms by which these histone mutations cause cancer are by and large unclear. Interestingly, two recent studies identified BS69/ZMYND11, which was proposed to be a candidate tumor suppressor, as a specific reader for a modified form of H3.3 (H3.3K36me3). Importantly, some H3.3 cancer mutations are predicted to abrogate the H3.3K36me3/BS69 interaction, suggesting that this interaction may play an important role in tumor suppression. These new findings also raise the question of whether H3.3 cancer mutations may lead to the disruption and/or gain of interactions of additional cellular factors that contribute to tumorigenesis.
authors.affiliation: Key Laboratory of Epigenetics of Shanghai Ministry of Education, School of Basic Medicine and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China; Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai 201102, China; yshi@hms.harvard.edu fei_lan@fudan.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Lan
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115; and Division of Newborn Medicine, Boston Children's Hospital, Boston MA 02115 yshi@hms.harvard.edu fei_lan@fudan.edu.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D020125:Mutation, Missense / Q000235:genetics; D009369:Neoplasms / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D006657:Histones; C094763:ZMYND11 protein, human
keywords: BS69; H3.3; H3.3K36me3; cancer; histone