The incorporation loci of H3.3K36M determine its preferential prevalence in chondroblastomas.
The incorporation loci of H3.3K36M determine its preferential prevalence in chondroblastomas.
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H3.3K36M 的掺入位点决定其在软骨母细胞瘤中优先流行
DOI：
10.1038/s41419-021-03597-9
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发表时间：
2021-03-24
影响因子：
9
通讯作者：
Fang D
中科院分区：
文献类型：
--
作者：
Zhang Y;Fang D
组蛋白H3.3K36M突变在90%以上的软骨母细胞瘤病例中被发现，它重新编程H3K36甲基化格局和基因表达以促进肿瘤的发生。然而，目前尚不清楚H3K36M突变是如何优先发生在软骨母细胞瘤的组蛋白H3变异体H3.3中的。在这里，我们报告了H3.3K36M-，而不是H3.1K36M-，突变细胞表现出更强的集落形成能力和分化缺陷。H3K36甲基化和增强子在H3.3K36M和H3.1K36M突变细胞中被重新编程为不同的状态。H3K36甲基化和增强子的重编程依赖于H3.3K36M和H3.1K36M所在的特定基因座。此外，针对染色质的H3K36M突变蛋白局部抑制了H3K36的甲基化。综上所述，这些结果突出了H3.3K36M突变蛋白的染色定位在表观基因组的重编程和随后的肿瘤发生中的作用，并揭示了H3K36M突变主要发生在软骨母细胞瘤的组蛋白H3.3中的分子机制。
The histone H3.3K36M mutation, identified in over 90% of chondroblastoma cases, reprograms the H3K36 methylation landscape and gene expression to promote tumorigenesis. However, it’s still unclear how the H3K36M mutation preferentially occurs in the histone H3 variant H3.3 in chondroblastomas. Here, we report that H3.3K36M-, but not H3.1K36M-, mutant cells showed increased colony formation ability and differentiation defects. H3K36 methylations and enhancers were reprogrammed to different status in H3.3K36M- and H3.1K36M-mutant cells. The reprogramming of H3K36 methylation and enhancers was depended on the specific loci at which H3.3K36M and H3.1K36M were incorporated. Moreover, targeting H3K36M-mutant proteins to the chromatin inhibited the H3K36 methylation locally. Taken together, these results highlight the roles of the chromatic localization of H3.3K36M-mutant protein in the reprogramming of the epigenome and the subsequent induction of tumorigenesis, and shed light on the molecular mechanisms by which the H3K36M mutation mainly occurs in histone H3.3 in chondroblastomas.
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影响因子：
16
作者：
Calo, Eliezer;Wysocka, Joanna
通讯作者：
Wysocka, Joanna
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
DOI：
10.1126/science.aac7272
发表时间：
2016-05-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lu C;Jain SU;Hoelper D;Bechet D;Molden RC;Ran L;Murphy D;Venneti S;Hameed M;Pawel BR;Wunder JS;Dickson BC;Lundgren SM;Jani KS;De Jay N;Papillon-Cavanagh S;Andrulis IL;Sawyer SL;Grynspan D;Turcotte RE;Nadaf J;Fahiminiyah S;Muir TW;Majewski J;Thompson CB;Chi P;Garcia BA;Allis CD;Jabado N;Lewis PW
通讯作者：
Lewis PW
影响因子：
--
作者：
Bradley, Elizabeth W.;Drissi, M. Hicham
通讯作者：
Drissi, M. Hicham
赖氨酸 36 处的组蛋白 H3 三甲基化引导 m(6)A RNA 共转录修饰
影响因子：
64.8
作者：
Huang, Huilin;Weng, Hengyou;Chen, Jianjun
通讯作者：
Chen, Jianjun