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多梳抑制复合物 CBX7 直接控制着 p16 基因座组蛋白 H3 赖氨酸 9 位的三甲基化。

Polycomb CBX7 directly controls trimethylation of histone H3 at lysine 9 at the p16 locus.

机构信息

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Etiology, Peking University Cancer Hospital and Institute, Beijing, China.

出版信息

PLoS One. 2010 Oct 29;5(10):e13732. doi: 10.1371/journal.pone.0013732.

DOI:10.1371/journal.pone.0013732
PMID:21060834
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2966406/
Abstract

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.

摘要

背景

H3K9 三甲基化（H3K9me3）和 PcG 抑制复合物-1（PRC1）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，这种三甲基化的起始机制尚不清楚。

方法/主要发现：在本研究中，我们发现上调胃癌细胞系 MGC803 和 BGC823 中 PRC1 成分 Cbx7 的表达，导致 p16-Arf-p15 基因座内的基因表达显著受到抑制。在 p16 启动子和调控区（RD）观察到 H3K9me3 的形成。在 CBX7 稳定上调的细胞中，也可以检测到 CBX7 和 SUV39H2 与这些区域的结合。双分子荧光互补测定（BiFC）观察到 CBX7-SUV39H2 复合物在核内。染色质结构域的突变或 Pc 盒的缺失消除了 CBX7 的结合和 H3K9me3 的形成，从而部分抑制了 CBX7 的功能。Suv39h2 的 siRNA 敲低阻断了 CBX7 对 p16 转录的抑制作用。此外，我们发现 CBX7 在伴有 p16 甲基化的胃癌组织中的表达明显低于其相应的正常组织，这与胃黏膜中 p16 的转录呈负相关。

结论/意义：这些结果首次表明，据我们所知，CBX7 可以在 p16 启动子处起始 H3K9me3 的形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/617f2c4608ff/pone.0013732.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/ec9b25571d11/pone.0013732.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/15cb6544769b/pone.0013732.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/ecf6c94541c6/pone.0013732.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/df5670d711f1/pone.0013732.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/f8de48717a44/pone.0013732.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/23780664f401/pone.0013732.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/debe0aac1a4f/pone.0013732.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/ada5262abd98/pone.0013732.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/789d34ef1280/pone.0013732.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/617f2c4608ff/pone.0013732.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/ec9b25571d11/pone.0013732.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/15cb6544769b/pone.0013732.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/ecf6c94541c6/pone.0013732.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/df5670d711f1/pone.0013732.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/f8de48717a44/pone.0013732.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/23780664f401/pone.0013732.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/debe0aac1a4f/pone.0013732.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/ada5262abd98/pone.0013732.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/789d34ef1280/pone.0013732.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b315/2966406/617f2c4608ff/pone.0013732.g010.jpg

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1
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2
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Cancer Res. 2009 Sep 1;69(17):7079-87. doi: 10.1158/0008-5472.CAN-09-1542. Epub 2009 Aug 25.
3
Methylation of p16 CpG island associated with malignant progression of oral epithelial dysplasia: a prospective cohort study.
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Front Cell Dev Biol. 2022 Sep 13;10:993525. doi: 10.3389/fcell.2022.993525. eCollection 2022.
4
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5
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6
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7
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