Harnessing of the nucleosome-remodeling-deacetylase complex controls lymphocyte development and prevents leukemogenesis.
Harnessing of the nucleosome-remodeling-deacetylase complex controls lymphocyte development and prevents leukemogenesis.
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DOI：
10.1038/ni.2150
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发表时间：
2011-11-13
影响因子：
30.5
通讯作者：
Georgopoulos, Katia
中科院分区：
文献类型：
--
作者：
Zhang, Jiangwen;Jackson, Audrey F.;Naito, Taku;Dose, Marei;Seavitt, John;Liu, Feifei;Heller, Elizabeth J.;Kashiwagi, Mariko;Yoshida, Toshimi;Gounari, Fotini;Petrie, Howard T.;Georgopoulos, Katia
细胞命运的决定取决于染色质调节因子和转录因子之间的相互作用。在这里，我们证明了Mi-2β核小体重塑和脱乙酰酶(NuRD)复合体的活性是由淋巴系决定蛋白的Ikaros家族控制的。Ikaros是淋巴细胞中NuRD复合体的组成部分，它将这个复合体与活跃的淋巴分化基因联系在一起。Ikaros DNA结合活性的丧失导致局部Mi-2β染色质重塑和组蛋白去乙酰化增加，并抑制淋巴基因的表达。NuRD复合体还重新分布到转录稳定的非Ikaros基因靶标上，参与增殖和新陈代谢，诱导它们重新激活。因此，从Ikaros调节释放NuRD阻止淋巴细胞成熟，并通过参与功能相反的表观遗传和遗传网络来调节进展到白血病状态。
Cell fate decisions depend on the interplay between chromatin regulators and transcription factors. Here we show that activity of the Mi-2β nucleosome remodeling and deacetylase (NuRD) complex was controlled by the Ikaros family of lymphoid-lineage determining proteins. Ikaros, an integral component of the NuRD complex in lymphocytes, tethered this complex to active lymphoid differentiation genes. Loss in Ikaros DNA binding activity caused a local increase in Mi-2β chromatin remodeling and histone deacetylation and suppression of lymphoid gene expression. The NuRD complex also redistributed to transcriptionally poised non-Ikaros gene targets, involved in proliferation and metabolism, inducing their reactivation. Thus, release of NuRD from Ikaros regulation blocks lymphocyte maturation and mediates progression to a leukemic state by engaging functionally opposing epigenetic and genetic networks.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
5.3
作者：
MOLNAR, A;GEORGOPOULOS, K
通讯作者：
GEORGOPOULOS, K
影响因子：
5.3
作者：
Arco, PGD;Koipally, J;Georgopoulos, K
通讯作者：
Georgopoulos, K
影响因子：
64.8
作者：
Mullighan, Charles G.;Goorha, Salil;Downing, James R.
通讯作者：
Downing, James R.
影响因子：
4
作者：
Gould, A
通讯作者：
Gould, A