Myc Regulates Chromatin Decompaction and Nuclear Architecture during B Cell Activation.
Myc Regulates Chromatin Decompaction and Nuclear Architecture during B Cell Activation.
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DOI：
10.1016/j.molcel.2017.07.013
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发表时间：
2017-08-17
期刊：
影响因子：
16
通讯作者：
Casellas R
中科院分区：
文献类型：
--
作者：
Kieffer-Kwon KR;Nimura K;Rao SSP;Xu J;Jung S;Pekowska A;Dose M;Stevens E;Mathe E;Dong P;Huang SC;Ricci MA;Baranello L;Zheng Y;Tomassoni Ardori F;Resch W;Stavreva D;Nelson S;McAndrew M;Casellas A;Finn E;Gregory C;St Hilaire BG;Johnson SM;Dubois W;Cosma MP;Batchelor E;Levens D;Phair RD;Misteli T;Tessarollo L;Hager G;Lakadamyali M;Liu Z;Floer M;Shroff H;Aiden EL;Casellas R
50年前，Vincent Allfrey及其同事发现淋巴细胞活化会引发染色质的大量乙酰化。然而，驱动表观遗传可及性的分子机制仍然未知。我们在这里表明，刺激淋巴细胞去致密染色质的三个差异调节的步骤。首先，染色质被重新定位远离核周边的全球乙酰化反应。第二，组蛋白纳米结构域簇通过需要Myc和持续能量输入的机制分解成单纤维。单分子成像表明，这一步骤降低了转录因子的停留时间和DNA靶点采样过程中的非特异性碰撞。第三，染色质相互作用从长程转变为短程为主，CTCF介导的环和接触结构域的数量翻了一番。这种结构变化促进了同源启动子-增强子的接触，也需要Myc和持续的ATP产生。因此，我们的研究结果定义的性质和转录的影响，染色质去凝聚，并揭示了一个意想不到的作用，Myc在哺乳动物细胞的核拓扑结构的建立。
50 years ago, Vincent Allfrey and colleagues discovered that lymphocyte activation triggers massive acetylation of chromatin. However, the molecular mechanisms driving epigenetic accessibility are still unknown. We here show that stimulated lymphocytes decondense chromatin by three differentially-regulated steps. First, chromatin is repositioned away from the nuclear periphery in response to global acetylation. Second, histone nanodomain clusters decompact into mononucleosome fibers through a mechanism that requires Myc and continual energy input. Single-molecule imaging shows that this step lowers transcription factor residence time and non-specific collisions during sampling for DNA targets. Third, chromatin interactions shift from long-range to predominantly short-range, and CTCF-mediated loops and contact domains double in numbers. This architectural change facilitates cognate promoter-enhancer contacts and also requires Myc and continual ATP production. Our results thus define the nature and transcriptional impact of chromatin decondensation and reveal an unexpected role for Myc in the establishment of nuclear topology in mammalian cells.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
48
作者：
Abrahamsson, Sara;Chen, Jiji;Hajj, Bassam;Stallinga, Sjoerd;Katsov, Alexander Y.;Wisniewski, Jan;Mizuguchi, Gaku;Soule, Pierre;Mueller, Florian;Darzacq, Claire Dugast;Darzacq, Xavier;Wu, Carl;Bargmann, Cornelia I.;Agard, David A.;Dahan, Maxime;Gustafsson, Mats G. L.
通讯作者：
Gustafsson, Mats G. L.
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64.5
作者：
Dowen JM;Fan ZP;Hnisz D;Ren G;Abraham BJ;Zhang LN;Weintraub AS;Schujiers J;Lee TI;Zhao K;Young RA
通讯作者：
Young RA
影响因子：
64.5
作者：
Gifford CA;Ziller MJ;Gu H;Trapnell C;Donaghey J;Tsankov A;Shalek AK;Kelley DR;Shishkin AA;Issner R;Zhang X;Coyne M;Fostel JL;Holmes L;Meldrim J;Guttman M;Epstein C;Park H;Kohlbacher O;Rinn J;Gnirke A;Lander ES;Bernstein BE;Meissner A
通讯作者：
Meissner A
影响因子：
64.5
作者：
Kouzine F;Wojtowicz D;Yamane A;Resch W;Kieffer-Kwon KR;Bandle R;Nelson S;Nakahashi H;Awasthi P;Feigenbaum L;Menoni H;Hoeijmakers J;Vermeulen W;Ge H;Przytycka TM;Levens D;Casellas R
通讯作者：
Casellas R