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


RESULTS
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.


CONCLUSIONS
These results demonstrated for the first time, to our knowledge, that CBX7 could initiate H3K9me3 formation at the p16 promoter.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Etiology, Peking University Cancer Hospital and Institute, Beijing, China.
Qiang
Q
Li
Xiuhong
X
Wang
Zheming
Z
Lu
Baozhen
B
Zhang
Zhenpo
Z
Guan
Zhaojun
Z
Liu
Qiming
Q
Zhong
Liankun
L
Gu
Jing
J
Zhou
Budong
B
Zhu
Jiafu
J
Ji
Dajun
D
Deng
D015153:Blotting, Western; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005453:Fluorescence; D019942:Genes, p16; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D012097:Repressor Proteins / Q000502:physiology*; D013274:Stomach Neoplasms / Q000378:metabolism
C503627:CBX7 protein, human; D006657:Histones; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1; D008239:Lysine