Histone H3.3 K27M and K36M mutations de-repress transposable elements through perturbation of antagonistic chromatin marks.
Histone H3.3 K27M and K36M mutations de-repress transposable elements through perturbation of antagonistic chromatin marks.
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DOI：
10.1016/j.molcel.2021.10.008
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发表时间：
2021-12-02
期刊：
影响因子：
16
通讯作者：
Jabado, Nada
中科院分区：
文献类型：
--
作者：
Chaouch, Amel;Berlandi, Johannes;Chen, Carol C. L.;Frey, Felice;Badini, Shireen;Harutyunyan, Ashot S.;Chen, Xiao;Krug, Brian;Hebert, Steven;Jeibmann, Astrid;Lu, Chao;Kleinman, Claudia L.;Hasselblatt, Martin;Lasko, Paul;Shirinian, Margret;Jabado, Nada
组蛋白H3.3赖氨酸到蛋氨酸的替换K27M和K36M削弱了相反的染色质标记H3K27me3/me2和H3K36me3/me2的沉积。我们发现，这些突变导致果蝇眼球原基营养不良和组织紊乱。H3K27me3在H3.3K27M中传播的限制及其在H3.3K36M中的重新分布导致了PRC2靶向的眼睛发育和包括krimp在内的piRNA生物发生基因的转录解除调控。值得注意的是，这两个突变体都促进了H3K36me2从重复区域到活性基因的重新分配，这与眼盘中反转录转座子的抑制有关。KRIMP的异常表达抑制了LINE反转录转座子，但不影响眼睛的表型。H3.3K27M的H3K36me2甲基转移酶ash1和H3.3K36M的PrC2组分E(Z)缺失，可以恢复眼发育基因的表达和正常的眼生长，表明拮抗标记的重新分布参与了K-to-M的发病。我们的结果暗示了H3K36me2的一种新功能，同时他们展示了针对相反表观遗传标记的癌组织蛋白的收敛下游效应。
Histone H3.3 Lysine-to-Methionine substitutions K27M and K36M impair the deposition of opposing chromatin marks, H3K27me3/me2 and H3K36me3/me2. We show that these mutations induce hypotrophic and disorganized eyes in Drosophila eye primordia. Restriction of H3K27me3 spread in H3.3K27M and its redistribution in H3.3K36M result in transcriptional deregulation of PRC2-targeted eye development and of piRNA biogenesis genes including krimp. Notably, both mutants promote redistribution of H3K36me2 away from repetitive regions into active genes, which associates with retrotransposon de-repression in eye discs. Aberrant expression of krimp represses LINE retrotransposons but does not contribute to the eye phenotype. Depletion of H3K36me2 methyltransferase ash1 in H3.3K27M, and of PRC2 component E(z) in H3.3K36M, restores the expression of eye developmental genes and normal eye growth, showing that redistribution of antagonistic marks contributes to K-to-M pathogenesis. Our results implicate a novel function for H3K36me2 while they showcase convergent downstream effects of oncohistones that target opposing epigenetic marks.
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影响因子：
9.2
作者：
Bourgey, Mathieu;Dali, Rola;Bourque, Guillaume
通讯作者：
Bourque, Guillaume
Mrg15 刺激果蝇中 Ash1 H3K36 甲基转移酶活性并促进 Ash1 Trithorax 组蛋白功能。
影响因子：
16.6
作者：
Huang C;Yang F;Zhang Z;Zhang J;Cai G;Li L;Zheng Y;Chen S;Xi R;Zhu B
通讯作者：
Zhu B
影响因子：
30.8
作者：
Behjati, Sam;Tarpey, Patrick S.;Presneau, Nadege;Scheipl, Susanne;Pillay, Nischalan;Van Loo, Peter;Wedge, David C.;Cooke, Susanna L.;Gundem, Gunes;Davies, Helen;Nik-Zainal, Serena;Martin, Sancha;McLaren, Stuart;Goodie, Victoria;Robinson, Ben;Butler, Adam;Teague, Jon W.;Halai, Dina;Khatri, Bhavisha;Myklebost, Ola;Baumhoer, Daniel;Jundt, Gernot;Hamoudi, Rifat;Tirabosco, Roberto;Amary, M. Fernanda;Futreal, P. Andrew;Stratton, Michael R.;Campbell, Peter J.;Flanagan, Adrienne M.
通讯作者：
Flanagan, Adrienne M.
DOI：
10.1126/science.1255104
发表时间：
2014-08-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Herz HM;Morgan M;Gao X;Jackson J;Rickels R;Swanson SK;Florens L;Washburn MP;Eissenberg JC;Shilatifard A
通讯作者：
Shilatifard A
影响因子：
4.6
作者：
Dorighi, Kristel M.;Tamkun, John W.
通讯作者：
Tamkun, John W.