组蛋白 H3.3 G34 突变在顺式中改变组蛋白 H3K36 和 H3K27 的甲基化。
Histone H3.3 G34 Mutations Alter Histone H3K36 and H3K27 Methylation In Cis.
机构信息
Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Dan L. Duncan Cancer Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
出版信息
J Mol Biol. 2018 May 25;430(11):1562-1565. doi: 10.1016/j.jmb.2018.04.014. Epub 2018 Apr 22.
Abstract
Histone H3 encoding genes, particularly H3F3A and H3F3B, the genes encoding the variant histone H3.3, are mutated at high frequency in pediatric brain and bone malignancies. Compared to the extensive studies on K27M and K36M mutations, little is known about the mechanism of G34 mutations found in pediatric glioblastoma or giant cell tumors of the bone. Here we report that unlike the K27M or K36M that affect global histone methylation, the giant cell tumors of the bone G34 mutations (G34L/W) only affect histone H3K36 and H3K27 methylation on the same mutated histone tails (in cis), a mechanism distinct from known histone mutations.
摘要
组蛋白 H3 编码基因，特别是编码变异组蛋白 H3.3 的 H3F3A 和 H3F3B 基因，在小儿脑和骨恶性肿瘤中高频突变。与对 K27M 和 K36M 突变的广泛研究相比，对于在小儿脑胶质瘤或骨巨细胞瘤中发现的 G34 突变的机制知之甚少。在这里，我们报告说，与影响全局组蛋白甲基化的 K27M 或 K36M 不同，骨巨细胞瘤的 G34 突变（G34L/W）仅影响同一突变组蛋白尾部（顺式）上的组蛋白 H3K36 和 H3K27 甲基化，这一机制不同于已知的组蛋白突变。
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1
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Genes Dev. 2016 Jul 15;30(14):1611-6. doi: 10.1101/gad.284323.116.
2
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Science. 2016 Jun 10;352(6291):1344-8. doi: 10.1126/science.aae0065. Epub 2016 May 26.
3
Histone H3K36 mutations promote sarcomagenesis through altered histone methylation landscape.组蛋白H3K36突变通过改变组蛋白甲基化格局促进肉瘤发生。
Science. 2016 May 13;352(6287):844-9. doi: 10.1126/science.aac7272.
4
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6
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Genes Dev. 2013 May 1;27(9):985-90. doi: 10.1101/gad.217778.113. Epub 2013 Apr 19.
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