Polycomb CBX7 directly controls trimethylation of histone H3 at lysine 9 at the p16 locus.
Polycomb CBX7 directly controls trimethylation of histone H3 at lysine 9 at the p16 locus.
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Polycomb CBX7 直接控制 p16 位点赖氨酸 9 处组蛋白 H3 的三甲基化
DOI：
10.1371/journal.pone.0013732
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发表时间：
2010-10-29
期刊：
影响因子：
3.7
通讯作者：
Deng D
中科院分区：
文献类型：
--
作者：
Li Q;Wang X;Lu Z;Zhang B;Guan Z;Liu Z;Zhong Q;Gu L;Zhou J;Zhu B;Ji J;Deng D
背景H3 K9三甲基化（H3 K9 me 3）和PcG阻遏复合物-1（PRC 1）的结合可能在p16基因的表观遗传沉默中发挥关键作用。然而，引发这种三甲基化的机制是未知的。方法/主要发现在本研究中，我们发现在胃癌细胞系MGC 803和BGC 823中上调PRC 1组分Cbx 7的表达导致p16-Arf-p15位点内基因的表达显著抑制。在p16启动子和调节结构域（RD）处观察到H3 K9 me 3形成。在CBX 7稳定上调的细胞中也可检测到CBX 7和SUV 39 H2与这些区域的结合。在双分子荧光互补分析（BiFC）中观察到CBX 7-SUV 39 H2复合物在细胞核内。染色体结构域的突变或PC盒的缺失消除了CBX 7的结合和H3 K9 me 3的形成，从而部分抑制了CBX 7的功能。Suv 39 h2的siRNA敲低阻断了CBX 7对p16转录的抑制作用。此外，我们还发现CBX 7在p16甲基化胃癌组织中的表达明显低于相应的正常组织，与p16在胃粘膜中的转录呈负相关。结论/意义据我们所知，这些结果首次证明CBX 7可以在p16启动子处启动H3 K9 me 3的形成。
Background H3K9 trimethylation (H3K9me3) and binding of PcG repressor complex-1 (PRC1) may play crucial roles in the epigenetic silencing of the p16 gene. However, the mechanism of the initiation of this trimethylation is unknown. Methodology/Principal Findings In the present study, we found that upregulating the expression of PRC1 component Cbx7 in gastric cancer cell lines MGC803 and BGC823 led to significantly suppress the expression of genes within the p16-Arf-p15 locus. H3K9me3 formation was observed at the p16 promoter and Regulatory Domain (RD). CBX7 and SUV39H2 binding to these regions were also detectable in the CBX7-stably upregulated cells. CBX7-SUV39H2 complexes were observed within nucleus in bimolecular fluorescence complementation assay (BiFC). Mutations of the chromodomain or deletion of Pc-box abolished the CBX7-binding and H3K9me3 formation, and thus partially repressed the function of CBX7. SiRNA-knockdown of Suv39h2 blocked the repressive effect of CBX7 on p16 transcription. Moreover, we found that expression of CBX7 in gastric carcinoma tissues with p16 methylation was significantly lower than that in their corresponding normal tissues, which showed a negative correlation with transcription of p16 in gastric mucosa. Conclusion/Significance These results demonstrated for the first time, to our knowledge, that CBX7 could initiate H3K9me3 formation at the p16 promoter.
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影响因子：
5.3
作者：
O'Carroll, D;Scherthan, H;Jenuwein, T
通讯作者：
Jenuwein, T
影响因子：
64.8
作者：
Gonzalez, S;Klatt, P;Serrano, M
通讯作者：
Serrano, M
影响因子：
11.2
作者：
Federico, Antonella;Pallante, Pierlorenzo;Fusco, Alfredo
通讯作者：
Fusco, Alfredo
影响因子：
11.2
作者：
Hahn MA;Hahn T;Lee DH;Esworthy RS;Kim BW;Riggs AD;Chu FF;Pfeifer GP
通讯作者：
Pfeifer GP
影响因子：
--
作者：
Hinz, S.;Kempkensteffen, C.;Weikert, S.
通讯作者：
Weikert, S.