TOP2 synergizes with BAF chromatin remodeling for both resolution and formation of facultative heterochromatin.
TOP2 synergizes with BAF chromatin remodeling for both resolution and formation of facultative heterochromatin.
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DOI：
10.1038/nsmb.3384
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发表时间：
2017-04
影响因子：
16.8
通讯作者：
Crabtree GR
中科院分区：
文献类型：
--
作者：
Miller EL;Hargreaves DC;Kadoch C;Chang CY;Calarco JP;Hodges C;Buenrostro JD;Cui K;Greenleaf WJ;Zhao K;Crabtree GR
兼性异染色质的分解和形成对发育、重编程和肿瘤发生至关重要。由于无法在体内研究异染色质动力学和结构，这些变化的机制知之甚少。我们设计了一种体内方法来研究这些机制，发现拓扑异构酶II（TOP 2），而不是TOP 1，与BAF协同作用（mSWI/SNF）ATP依赖性染色质重塑复合物在全基因组范围内将兼性异染色质解析为可接近的染色质，而不依赖于转录，表明DNA拓扑结构的变化通过（去-）异染色质分解需要的是连锁而不是通过旋转释放扭转应力。反过来，TOP 2和BAF合作招募多能性因子，解释了BAF复合物的一些指导作用。出乎意料的是，我们发现TOP2也在兼性异染色质的重组中起作用，这表明兼性异染色质和可接近染色质存在于不同的连锁状态或其他拓扑结构，这可能对它们的结构至关重要。
Resolution and formation of facultative heterochromatin is essential to development, reprogramming, and oncogenesis. The mechanisms underlying these changes are poorly understood due to the inability to study heterochromatin dynamics and structure in vivo. We devised an in vivo approach to investigate these mechanisms and found that topoisomerase II (TOP2), but not TOP1, synergizes with BAF (mSWI/SNF) ATP-dependent chromatin remodeling complexes genome-wide to resolve facultative heterochromatin to accessible chromatin independent of transcription, indicating that changes in DNA topology through (de-)catenation rather than release of torsional stress through swiveling is necessary for heterochromatin resolution. In turn, TOP2 and BAF cooperate to recruit pluripotency factors, explaining some of the instructive roles of BAF complexes. Unexpectedly, we found that TOP2, also plays a role in the reformation of facultative heterochromatin, suggesting that facultative heterochromatin and accessible chromatin exist at different states of catenation or other topologies, which may be critical to their structures.