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


ABSTRACT: 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.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.These results demonstrated for the first time, to our knowledge, that CBX7 could initiate H3K9me3 formation at the p16 promoter.

SUBMITTER: Li Q 

PROVIDER: S-EPMC2966406 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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

Li Qiang Q   Wang Xiuhong X   Lu Zheming Z   Zhang Baozhen B   Guan Zhenpo Z   Liu Zhaojun Z   Zhong Qiming Q   Gu Liankun L   Zhou Jing J   Zhu Budong B   Ji Jiafu J   Deng Dajun D  

PloS one 20101029 10


<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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. H3K9m  ...[more]

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