The Study Of HINO80/YY1 Chromatin Remodeling Complex On BBBIP Transactivation

INO80 chromatin remodeling enzyme is a member of SWI/SNF superfamily,it contains an ATPase domain and acts as the core subunit of INO80 chromatin remodeling complex.With the help of ATP,INO80 chromatin remodeling complex could cause nucleosome sliding on DNA strands,then change the density of nucleosome and the accessibility of DNA.Furthermore,INO80 chromatin remodeling complex can change the chromatin structure by replacing the histone variant.YY1 is a ubiquitously expressed transcription factor,it can recruit to the promoter region and regulate gene expression.Meanwhile,as a important subunit of INO80 chromatin remodeling complex,YY1 participates in recruiting to target DNA site and regulating the chromatin structure,together with other subunits.In eukaryotes,DNA is wrapped in chromatin,which barrier the interaction of DNA with relevant factors,thereby inhibiting the DNA-related biological processes.Owing to its function of changing the chromatin structure,INO80/YY1 chromatin remodeling complex plays a important role in DNA replication,damage repair and transcription regulation processes.BCCIP is a BRCA2(breast cancer susceptibility gene 2)and CDKN1A(cyclin-dependent kinase inhibitor 1A)interacting protein,it contains two isoforms,BCCIP? and BCCIP?,which are different only in the C-terminal variable domain.BCCIP takes part in many essential cellular progresses by interacting with BRCA2 and p21.For example,BCCIP helps maintain the transactivation of p53 and increases the p21 protein level,so that regulating the cell cycle.BCCIP also has critical roles in keeping the genome stability and chromatin integrity while it interacts with BRCA2,which is involved in homologous recombination repair.Moreover,BCCIP can inhibit the mammary tumorigenesis as a tumor suppressor.Recent studies showed that BCCIP is downregulated in multiple clinically diagnostic primary tumor issues,but the mechanism of how BCCIP is regulated remains unclear.Our previous studies showed that INO80 knockdown leads to decrease of BCCIP expression.Others reported that the BCCIP promoter region may contain a YY1 binding site.Herein we speculated the INO80/YY1 chromatin remodeling complex is likely to interact with the BCCIP promoter region and then transactivate BCCIP expression.By using the luciferase report assay system,we discovered that YY1 and other INO80 chromatin remodeling complex subunits can activate BCCIP transcription and increase its protein level.Our study revealed the important role of INO80/YY1 chromatin remodeling complex in upregulating BCCIP,laid the foundations of elucidating the effects and its mechanisms of BCCIP in tumorigenesis.