Chromatin organization changes during the establishment and maintenance of the postmitotic state.
Chromatin organization changes during the establishment and maintenance of the postmitotic state.
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DOI：
10.1186/s13072-017-0159-8
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发表时间：
2017-11-10
影响因子：
3.9
通讯作者：
Buttitta L
中科院分区：
文献类型：
--
作者：
Ma Y;Buttitta L
随着细胞分化，基因组组织在发育过程中发生变化。随着细胞的发育潜能受到限制，染色质运动变得越来越受限，异染色质聚集。这些变化与细胞周期的减慢相一致，这也会影响染色质的组织和动力学。终末分化通常伴随着细胞周期的永久退出，现有的数据表明有丝分裂后细胞中抑制性染色质结构和细胞周期沉默之间存在密切关系。异染色质聚集也可能有助于稳定的基因抑制，以维持终末分化或细胞周期退出，但是否聚类是由分化，细胞周期的变化，或两者都不清楚。在这里，我们研究染色质组织，终末分化和细胞周期退出之间的关系。我们把我们的研究集中在果蝇翅膀，上皮细胞从活跃的增殖过渡到有丝分裂后的状态在一个时间控制的方式。我们发现在这个组织中有两个阶段的G 0，一个是灵活的G 0期，在特定的遗传操作下，细胞可以被诱导重新进入细胞周期，另一个是我们称之为“鲁棒”的状态，在这种状态下，细胞对细胞周期的重新进入变得非常顽固。通过驱动细胞周期激活剂的异位表达而损害灵活的G 0导致异染色质相关组蛋白修饰（如H3 K27三甲基化和H3 K9三甲基化）以及它们相关的阻遏物Polycomb和异染色质蛋白1（HP 1）的聚集的全局破坏。然而，这种破坏是可逆的。当细胞进入一个强大的G 0状态，即使在异位细胞周期活动的存在下，异染色质相关的修饰的聚类恢复。如果细胞周期出口被绕过，翼中的细胞继续终末分化，但异染色质聚集被严重破坏。异染色质依赖性基因沉默似乎不是细胞周期退出所需的，因为即使面对正常致癌细胞周期活性，损害zeste的H3 K27甲基转移酶增强子和/或HP 1也不能阻止稳健的细胞周期退出。在终末分化过程中异染色质聚集是细胞周期退出的结果，而不是分化。妥协异染色质依赖性基因沉默不破坏细胞周期退出。本文的在线版本（10.1186/s13072-017-0159-8）包含补充材料，可供授权用户使用。
Genome organization changes during development as cells differentiate. Chromatin motion becomes increasingly constrained and heterochromatin clusters as cells become restricted in their developmental potential. These changes coincide with slowing of the cell cycle, which can also influence chromatin organization and dynamics. Terminal differentiation is often coupled with permanent exit from the cell cycle, and existing data suggest a close relationship between a repressive chromatin structure and silencing of the cell cycle in postmitotic cells. Heterochromatin clustering could also contribute to stable gene repression to maintain terminal differentiation or cell cycle exit, but whether clustering is initiated by differentiation, cell cycle changes, or both is unclear. Here we examine the relationship between chromatin organization, terminal differentiation and cell cycle exit. We focused our studies on the Drosophila wing, where epithelial cells transition from active proliferation to a postmitotic state in a temporally controlled manner. We find there are two stages of G0 in this tissue, a flexible G0 period where cells can be induced to reenter the cell cycle under specific genetic manipulations and a state we call “robust,” where cells become strongly refractory to cell cycle reentry. Compromising the flexible G0 by driving ectopic expression of cell cycle activators causes a global disruption of the clustering of heterochromatin-associated histone modifications such as H3K27 trimethylation and H3K9 trimethylation, as well as their associated repressors, Polycomb and heterochromatin protein 1 (HP1). However, this disruption is reversible. When cells enter a robust G0 state, even in the presence of ectopic cell cycle activity, clustering of heterochromatin-associated modifications is restored. If cell cycle exit is bypassed, cells in the wing continue to terminally differentiate, but heterochromatin clustering is severely disrupted. Heterochromatin-dependent gene silencing does not appear to be required for cell cycle exit, as compromising the H3K27 methyltransferase Enhancer of zeste, and/or HP1 cannot prevent the robust cell cycle exit, even in the face of normally oncogenic cell cycle activities. Heterochromatin clustering during terminal differentiation is a consequence of cell cycle exit, rather than differentiation. Compromising heterochromatin-dependent gene silencing does not disrupt cell cycle exit. The online version of this article (10.1186/s13072-017-0159-8) contains supplementary material, which is available to authorized users.
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DOI：
10.1083/jcb.149.4.811
发表时间：
2000-05-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Freeman L;Aragon-Alcaide L;Strunnikov A
通讯作者：
Strunnikov A
癌基因诱导的DNA损伤反应与衰老和癌症异染色质之间的相互作用。
影响因子：
21.3
作者：
Di Micco R;Sulli G;Dobreva M;Liontos M;Botrugno OA;Gargiulo G;dal Zuffo R;Matti V;d'Ario G;Montani E;Mercurio C;Hahn WC;Gorgoulis V;Minucci S;d'Adda di Fagagna F
通讯作者：
d'Adda di Fagagna F
视网膜母细胞瘤抑制组蛋白H3赖氨酸27的蛋白质依赖性甲基化与不可逆的细胞周期出口有关。
影响因子：
7.8
作者：
Blais, Alexandre;van Oevelen, Chris J. C.;Margueron, Raphael;Acosta-Alvear, Diego;Dynlacht, Brian David
通讯作者：
Dynlacht, Brian David
影响因子：
3.3
作者：
Evertts AG;Manning AL;Wang X;Dyson NJ;Garcia BA;Coller HA
通讯作者：
Coller HA
影响因子：
64.8
作者：
Ho, Joshua W. K.;June, Youngsook L.;Liu, Tao;Alver, Burak H.;Lee, Soohyun;Ikegami, Kohta;Sohn, Kyung-Ah;Minoda, Aki;Tolstorukov, Michael Y.;Appert, Alex;Parker, Stephen C. J.;Gu, Tingting;Kundaje, Anshul;Riddle, Nicole C.;Bishop, Eric;Egelhofer, Thea A.;Hu, Sheng'en Shawn;Alekseyenko, Artyom A.;Rechtsteiner, Andreas;Asker, Dalal;Belsky, Jason A.;Bowmanm, Sarah K.;Chens, Q. Brent;Chen, Ron A. -J.;Day, Daniel S.;Dong, Yan;Dose, Andrea C.;Duan, Xikun;Epstein, Charles B.;Ercan, Sevinc;Feingold, Elise A.;Ferrari, Francesco;Garrigues, Jacob M.;Gehlenborg, Nils;Good, Peter J.;Haseley, Psalm;He, Daniel;Herrmann, Moritz;Hoffman, Michael M.;Jeffers, Tess E.;Kharchenko, Peter V.;Kolasinska-Zwierz, Paulina;Kotwaliwale, Chitra V.;Kumar, Nischay;Langley, Sasha A.;Larschan, Erica N.;Latorre, Isabel;Libbrecht, Maxwell W.;Lin, Xueqiu;Park, Richard;Pazin, Michael J.;Pham, Hoang N.;Plachetka, Annette;Qin, Bo;Schwartz, Yuri B.;Shoresh, Noam;Stempor, Przemyslaw;Vielle, Anne;Wang, Chengyang;Whittle, Christina M.;Xue, Huiling;Kingstonm, Robert E.;Kim, Ju Han;Bernstein, Bradley E.;Dernburg, Abby F.;Pirrotta, Vincenzo;Kuroda, Mitzi I.;Noble, William S.;Tullius, Thomas D.;Kellis, Manolis;MacAlpine, David M.;Strome, Susan;Elgin, Sarah C. R.;Liu, Xiaole Shirley;Lieb, Jason D.;Ahringer, Julie;Karpen, Gary H.;Park, Peter J.
通讯作者：
Park, Peter J.