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Updated: Mar 16, 2026

Generation and Purification of Human INO80 Chromatin Remodeling Complexes and Subcomplexes
Published on: October 23, 2014
Human INO80/YY1 chromatin remodeling complex transcriptionally regulates the BRCA2- and CDKN1A-interacting protein
Jiaming Su1, Yi Sui1, Jian Ding1
1School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, 130012, China.
Abstract:
The BCCIP (BRCA2- and CDKN1A-interacting protein) is an important cofactor for BRCA2 in tumor suppression. Although the low expression of BCCIP is observed in multiple clinically diagnosed primary tumor tissues such as ovarian cancer, renal cell carcinoma and colorectal carcinoma, the mechanism of how BCCIP is regulated in cells is still unclear. The human INO80/YY1 chromatin remodeling complex composed of 15 subunits catalyzes ATP-dependent sliding of nucleosomes along DNA. Here, we first report that BCCIP 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 BCCIP 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 BCCIP promoter region. Our findings strongly indicate that BCCIP is a potential target gene of the INO80/YY1 complex.
Insights
BRCA2- and CDKN1A-interacting protein (BCCIP) is crucial for tumor suppression. This study reveals BCCIP is a novel target gene of the INO80/YY1 chromatin remodeling complex, clarifying its cellular regulation mechanism.
Area of Science:
- Molecular Biology
- Cancer Research
- Chromatin Biology
Background:
- BCA2- and CDKN1A-interacting protein (BCCIP) is a tumor suppressor cofactor with low expression in various cancers.
- The precise regulatory mechanisms of BCCIP expression in cells remain largely unknown.
- The INO80/YY1 complex is a human chromatin remodeling complex involved in nucleosome dynamics.
Purpose of the Study:
- To investigate and identify novel regulators of BCCIP expression.
- To determine if the INO80/YY1 complex targets BCCIP.
- To elucidate the mechanism by which INO80/YY1 influences BCCIP gene expression.
Main Methods:
- Gene expression analysis and siRNA knockdown experiments to identify candidate genes.
- Luciferase reporter assays to assess transcriptional regulation.
- Chromatin immunoprecipitation (ChIP) assays to determine protein-DNA interactions.
Main Results:
- Gene expression studies and siRNA knockdown identified BCCIP as a target of the INO80/YY1 complex.
- Silencing or overexpressing INO80/YY1 subunits altered BCCIP mRNA and protein levels.
- ChIP assays confirmed enrichment of INO80 and YY1 at the BCCIP promoter, dependent on both proteins.
Conclusions:
- BCCIP is a novel target gene of the human INO80/YY1 chromatin remodeling complex.
- The INO80/YY1 complex plays a critical role in regulating BCCIP gene expression.
- These findings provide new insights into the regulation of BCCIP and its role in tumor suppression.
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