BCCIP Binds To And Activates Its Promoter In A YY1-dependent Fashion In HCT116 Cells

Epigenetics(epigenetics)is a discipline that emerged gradually in the 1980 s.Epigenetics has been developed gradually in many genetic processes that are inconsistent with the classical genetic laws of Mendelian genetics.Epigenetics is a branch of genetics that allows for genetic changes in gene expression without changes in the nucleotide sequence of the genome.This paper focuses on the regulation of human INO80/YY1 chromatin remoting complex by tumor suppressor gene BCCIP.BCCIP(BRCA2 and CDKN1 A interacting protein)is a protein that interacts with breast cancer susceptibility gene 2(BRCA2)and p21(cyclin-dependent kinase inhibitor 1A,CDKN1A).It plays an important role in cell mitosis,cell cycle regulation,cytokinesis,DNA homologous recombination repair,genome stability,and involved in gene transcription regulation.As a member of the gli-kruppel family,YY1 was originally considered as a DNA-binding protein,with the deep study we found that YY1 is a specific subunit of human INO80 chromatin remodeling complex.Participate in the regulation of various cellular processes.Since YY1 contains both transcriptional activation region and transcriptional inhibition region,it can extensively regulate the transcriptional activity of genes.Numerous studies have shown that YY1 can regulate the activation or inhibition of gene transcription by recruiting different transcription factors to different regions of YY1.BCCIP was regulated by INO80/YY1 complexThe restriction of Yin Yang 1(YY1)at BRCA2 and CDKN1A/p21-interacting protein(BCCIP)transcriptional start site(TSS)proximal region in several human cancer cell lines was found by analyzation of ChIP-Seq database from UCSC Genome Browser(http://genome.ucsc.edu).However,whether the stabilization of YY1 by BCCIP impacts its recruitment in the BCCIP promoter region is unclear.Here,we present evidence that transcriptional regulation of YY1 on BCCIP is closely related to YY1 stability in HCT116 human colon cancer cells.YY1 stabilization was in turn regulated by BCCIP,suggesting the existence of a BCCIP–YY1 feedback loop in regulating BCCIP transcription by the YY1.Overexpression of BCCIP stabilized YY1 while knockdown of BCCIP reduced YY1 protein level.In addition,direct interaction between YY1 and BCCIP was confirmed by coimmunoprecipitation approach.Also,the N-terminus region of BCCIP,including the internal conserved domain(ICD),was responsible for binding with the amino acid 146–270 of YY1.More importantly,YY1 stability was related to the BCCIP/ICD domain-mediated YY1 ubiquitination pathway.Moreover,a limited BCCIP promoter region containing YY1 binding site(CCGCCATC)was tightly associated with the pGL4-BCCIP-Luc luciferase activity.In ChIP assays,shBCCIP lentiviral-mediated YY1 instability decreased recruitment of the YY1 at BCCIP TSS proximal region,which could not be restored by YY1 overexpression.Furthermore,knockdown of YY1 inhibited the binding of BCCIP itself at BCCIP promoter region proximal to TSS,demonstrating that transcriptional regulation of the YY1 on BCCIP can be modulated by BCCIP itself in a YY1-dependent fashion.