摘要
The BCCIP （BRCA2. and CDKNIA-interacting protein） is an important cofactor for BRCA2 in tumor suppression. Although the low expression of BCClP is observed in multiple clinically diagnosed primary tumor tissues such as ovarian cancer, renal cell carcinoma and col- orectal carcinoma, the mechanism of how BCCIP is regulated in cells is still unclear. The human INO80/YY1 chromatin remodeling complex composed of 15 sub- units catalyzes ATP-dependent sliding of nucleosomes along DNA. Here, we first report that BCClP is a novel target gene of the INO80/YY1 complex by presenting a series of experimental evidence. Gene expression studies combined with siRNA knockdown data locked candidate genes including BCCIP of the INO80/YY1 complex. Silencing or over-expressing the subunits of the INO80/YY1 complex regulates the expression level of BCCIP both in mRNA and proteins in cells. Also, the functions of INO80/YY1 complex in regulating the transactivation of BCCIP were confirmed by luciferase reporter assays. Chromatin immunoprecipitation （CHIP） experiments clarify the enrichment of INO80 and YY1 at ＋0.17 kb downstream of the BCClP transcriptional start site. However, this enrichment is significantly inhibited by either knocking down INO80 or YY1, suggesting the existence of both INO80 and YY1 is required for recruiting the INO80/YY1 complex to BCClP promoter region. Our findings strongly indicate that BCClP is a potential target gene of the INO80/YY1 complex.
The BCCIP （BRCA2. and CDKNIA-interacting protein） is an important cofactor for BRCA2 in tumor suppression. Although the low expression of BCClP is observed in multiple clinically diagnosed primary tumor tissues such as ovarian cancer, renal cell carcinoma and col- orectal carcinoma, the mechanism of how BCCIP is regulated in cells is still unclear. The human INO80/YY1 chromatin remodeling complex composed of 15 sub- units catalyzes ATP-dependent sliding of nucleosomes along DNA. Here, we first report that BCClP is a novel target gene of the INO80/YY1 complex by presenting a series of experimental evidence. Gene expression studies combined with siRNA knockdown data locked candidate genes including BCCIP of the INO80/YY1 complex. Silencing or over-expressing the subunits of the INO80/YY1 complex regulates the expression level of BCCIP both in mRNA and proteins in cells. Also, the functions of INO80/YY1 complex in regulating the transactivation of BCCIP were confirmed by luciferase reporter assays. Chromatin immunoprecipitation （CHIP） experiments clarify the enrichment of INO80 and YY1 at ＋0.17 kb downstream of the BCClP transcriptional start site. However, this enrichment is significantly inhibited by either knocking down INO80 or YY1, suggesting the existence of both INO80 and YY1 is required for recruiting the INO80/YY1 complex to BCClP promoter region. Our findings strongly indicate that BCClP is a potential target gene of the INO80/YY1 complex.
基金
This work was supported by the National Natural Science Foundation of China （Grant Nos. 31071131 and 31171245）, by the National Laboratory of Biomacromolecules （O5SY02110A and 2012kf04）, and by the Project of Jilin Province Science and Technology Development Program （20130413002GH）.
