Spatial interplay between Polycomb and Trithorax complexes controls transcriptional activity in T lymphocytes.
Spatial interplay between Polycomb and Trithorax complexes controls transcriptional activity in T lymphocytes.
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Polycomb 和 Trithorax 复合体之间的空间相互作用控制 T 淋巴细胞的转录活性。
DOI：
10.1128/mcb.00677-15
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
T.
中科院分区：
文献类型：
--
作者：
Onodera;A.;Tumes;D. J.;Watanabe;Y.;Hirahara;K.;Kaneda;A.;Sugiyama;F.;Suzuki;Y.;and Nakayama;T.
TrxG和PcG蛋白是两种相互拮抗的染色质修饰复合物，然而，它们如何共同介导转录反调节仍然是未知的。全基因组分析显示，结合Ezh2和menin，中央成员的PcG和TrxG复合物，分别是密切相关的。此外，我们确定了一个发展变化的定位EZH2和menin在分化的T淋巴细胞相比，胚胎干细胞。转录起始位点上游的Ezh2结合和下游的menin结合经常出现在转录水平较高的基因中，而下游的Ezh2结合和上游的menin结合则出现在T淋巴细胞中表达较低的基因中。有趣的是，在Ezh2和menin共占据的基因中，那些在相同位置表现出占据的基因显示出对Ezh2缺失的极大增强的敏感性。最后，我们还发现Ezh2和menin占有率的不同组合与对T细胞发育重要的特定功能基因组的表达相关。因此，空间合作基因调控的PcG和TrxG复合物可能代表了一种新的机制，调节分化细胞的转录身份。
Trithorax group (TrxG) and Polycomb group (PcG) proteins are two mutually antagonistic chromatin modifying complexes, however, how they together mediate transcriptional counter-regulation remains unknown. Genome-wide analysis revealed that binding of Ezh2 and menin, central members of the PcG and TrxG complexes, respectively, were reciprocally correlated. Moreover, we identified a developmental change in the positioning of Ezh2 and menin in differentiated T lymphocytes compared to embryonic stem cells. Ezh2-binding upstream and menin-binding downstream of the transcription start site was frequently found at genes with higher transcriptional levels, and Ezh2-binding downstream and menin-binding upstream was found at genes with lower expression in T lymphocytes. Interestingly, of the Ezh2 and menin cooccupied genes, those exhibiting occupancy at the same position displayed greatly enhanced sensitivity to loss of Ezh2. Finally, we also found that different combinations of Ezh2 and menin occupancy were associated with expression of specific functional gene groups important for T cell development. Therefore, spatial cooperative gene regulation by the PcG and TrxG complexes may represent a novel mechanism regulating the transcriptional identity of differentiated cells.