Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells.
Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells.
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DOI：
10.1038/s41467-018-06092-6
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发表时间：
2018-09-07
影响因子：
16.6
通讯作者：
Aboobaker AA
中科院分区：
文献类型：
--
作者：
Mihaylova Y;Abnave P;Kao D;Hughes S;Lai A;Jaber-Hijazi F;Kosaka N;Aboobaker AA
目前，对动物干细胞表观遗传调控的进化知之甚少。在这里，我们证明，使用真涡虫干细胞系统调查的作用的COMPASS家庭的MLL 3/4组蛋白甲基转移酶，其功能作为肿瘤抑制剂在哺乳动物干细胞是保守的，在很长的进化距离。为了研究动物干细胞中全基因组表观遗传调控程序的潜在保守性，我们通过对G2/M涡虫干细胞群体进行RNA-seq和ChIP-seq来评估Mll 3/4功能丧失的影响，其中部分有助于形成生长物。我们在受影响的基因中发现了许多癌基因和肿瘤抑制基因，这些基因可能是介导MLL 3/4肿瘤抑制功能的候选基因。我们的工作证明了动物中一个重要的表观遗传调控程序的保护，并强调了研究表观遗传调控的涡虫模型系统的实用性。M113/4组蛋白甲基转移酶可以在人类中充当肿瘤抑制剂。在这里，作者在Planarian Schmidtea mediterranea中鉴定了哺乳动物MLL 3/4的三个直系同源物，并表明敲除会导致再生动物的生长，这表明这些基因的肿瘤抑制功能是高度保守的。
Currently, little is known about the evolution of epigenetic regulation in animal stem cells. Here we demonstrate, using the planarian stem cell system to investigate the role of the COMPASS family of MLL3/4 histone methyltransferases that their function as tumor suppressors in mammalian stem cells is conserved over a long evolutionary distance. To investigate the potential conservation of a genome-wide epigenetic regulatory program in animal stem cells, we assess the effects of Mll3/4 loss of function by performing RNA-seq and ChIP-seq on the G2/M planarian stem cell population, part of which contributes to the formation of outgrowths. We find many oncogenes and tumor suppressors among the affected genes that are likely candidates for mediating MLL3/4 tumor suppression function. Our work demonstrates conservation of an important epigenetic regulatory program in animals and highlights the utility of the planarian model system for studying epigenetic regulation. The Mll3/4 histone methyltransferases can act as tumour suppressors in humans. Here, the authors identify three orthologs of mammalian MLL3/4 in the planarian Schmidtea mediterranea and show that knockdown causes outgrowths in regenerating animals, suggesting that the tumour suppressive function of these genes is deeply conserved.
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影响因子：
9.8
作者：
Gallego-Ortega D;Ledger A;Roden DL;Law AM;Magenau A;Kikhtyak Z;Cho C;Allerdice SL;Lee HJ;Valdes-Mora F;Herrmann D;Salomon R;Young AI;Lee BY;Sergio CM;Kaplan W;Piggin C;Conway JR;Rabinovich B;Millar EK;Oakes SR;Chtanova T;Swarbrick A;Naylor MJ;O'Toole S;Green AR;Timpson P;Gee JM;Ellis IO;Clark SJ;Ormandy CJ
通讯作者：
Ormandy CJ
影响因子：
5.3
作者：
Hsieh, JJD;Ernst, P;Korsmeyer, SJ
通讯作者：
Korsmeyer, SJ
影响因子：
4.6
作者：
Currie, Ko W.;Pearson, Bret J.
通讯作者：
Pearson, Bret J.
成年干细胞多能与DNA甲基化独立于成年干细胞多能性是必需的。
影响因子：
2.7
作者：
Jaber-Hijazi, Farah;Lo, Priscilla J. K. P.;Mihaylova, Yuliana;Foster, Jeremy M.;Benner, Jack S.;Romero, Belen Tejada;Chen, Chen;Malla, Sunir;Solana, Jordi;Ruzov, Alexey;Aboobaker, A. Aziz
通讯作者：
Aboobaker, A. Aziz
影响因子：
64.8
作者：
Compagno, Mara;Lim, Wei Keat;Grunn, Adina;Nandula, Subhadra V.;Brahmachary, Manisha;Shen, Qiong;Bertoni, Francesco;Ponzoni, Maurilio;Scandurra, Marta;Califano, Andrea;Bhagat, Govind;Chadburn, Amy;Dalla-Favera, Riccardo;Pasqualucci, Laura
通讯作者：
Pasqualucci, Laura