Negative Regulation of p21Waf1/Cip1 by Human INO80 Chromatin Remodeling Complex Is Implicated in Cell Cycle Phase G2/M Arrest and Abnormal Chromosome Stability

Cao, Lingling; Ding, Jian; Dong, Liguo; Zhao, Junjun; Su, Jiaming; Wang, Lingyao; Sui, Yi; Zhao, Tong; Wang, Fei; Jin, Jingji; Cai, Yong

doi:10.1371/journal.pone.0137411

Cited by 20 publications

(29 citation statements)

References 45 publications

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“…1H. In agreement with our previous report [20], upregulation of p21 in both mRNA and proteins was observed by knocking down INO80 with siRNA at 0 h of Doxo treatment ( Fig. 1I-K).…”

Section: Doxo-induced P21 Expression Was Regulated By Human Ino80 Chrsupporting

confidence: 92%

“…1C,D). In agreement with our previous report [20], upregulation of p21 in both mRNA and proteins was observed by knocking down INO80 with siRNA at 0 h of Doxo treatment (Fig. To further understand the effect of 0.5 lM Doxo on the cell cycle, fluorescenceactivated cell sorting (FACS) analysis was performed at different times (Fig.…”

Section: Doxo-induced P21 Expression Was Regulated By Human Ino80 Chrsupporting

confidence: 89%

“…Therefore, knockdown of INO80 released this inhibitory effect on the promoter region and caused p21 expression. For example, Genotoxic agents induced p53-serine 15 phosphorylation (p53S15P) is required for efficient recruitment of p53 to chromatin [20,35]. However, when cells are exposed to genotoxic agents such as UV light and Doxo, p53 protein is activated via phosphorylation and binds to p53-responsive elements of the p21 gene [35].…”

Section: Discussionmentioning

confidence: 99%

“…The PCR reactions were conducted as previously described [20]. cDNA synthesis was done with PrimeScript 1st Strand cDNA synthesis Kit (Takara).…”

Section: Quantitative Real-time Pcrmentioning

confidence: 99%

“…Two highly conserved p53 response elements (PRE) in the p21 promoter region can be recognized and bound by activated tumor suppressor p53 to induce transcriptional activation of the p21 gene [19]. The INO80 complex not only occupies p53-binding sites of the p21 promoter, but also negatively regulates p21 expression in a p53-dependent manner [20]. Meantime, expression of p21 is associated with localization of H2A.Z, and dynamics of H2A.Z loci are regulated by chromatin remodelers via catalyzing nucleosome sliding and exchange of H2A.Z with H2A.…”

Section: Introductionmentioning

confidence: 99%

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The chromatin remodeling protein INO80 contributes to the removal of H2A.Z at the p53‐binding site of the p21 gene in response to doxorubicin

Ding

Sui

et al. 2018

The FEBS Journal

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Transcriptional activation of p21 (cyclin-dependent kinase inhibitor 1A) due to DNA damage often alters the distribution of histone variant H2A.Z at the p21 gene. However, whether the human INO80 complex regulates changes in H2A.Z at the p21 promoter is unclear. We show here that activation of p21 expression by doxorubicin (Doxo) in U2OS cells is required for removal of H2A.Z by INO80 at the p53-binding site proximal region (-2.2 kb) of the p21 promoter. A purified INO80 complex, but not the INO80E653Q mutant-complex, which lost DNA-sliding activity, is mainly responsible for removing H2A.Z from reconstituted nucleosomes in vitro. This activity was enhanced with MOF-mediated histone acetylation, suggesting that INO80 more readily removes H2A.Z from loosened nucleosomes. Also, co-occupancy of INO80 and H2A.Z -2.2 kb upstream of the p21 transcriptional start site (TSS) was observed. H2A.Z at this region was removed in a short time after Doxo treatment and activated p21 expression. However, p21 induction was inhibited by INO80 knockdown by delaying H2A.Z removal, indicating the need for INO80. Moreover, shMOF-mediated histone acetylation reduced recruitment of INO80 -2.2 kb upstream of p21 TSS and inhibited the removal of H2A.Z in Doxo-treated cells. These data provide new insights into the transcriptional regulation of p21 by the INO80 complex.

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“…1H. In agreement with our previous report [20], upregulation of p21 in both mRNA and proteins was observed by knocking down INO80 with siRNA at 0 h of Doxo treatment ( Fig. 1I-K).…”

Section: Doxo-induced P21 Expression Was Regulated By Human Ino80 Chrsupporting

confidence: 92%

Section: Doxo-induced P21 Expression Was Regulated By Human Ino80 Chrsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

“…The PCR reactions were conducted as previously described [20]. cDNA synthesis was done with PrimeScript 1st Strand cDNA synthesis Kit (Takara).…”

Section: Quantitative Real-time Pcrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The chromatin remodeling protein INO80 contributes to the removal of H2A.Z at the p53‐binding site of the p21 gene in response to doxorubicin

Ding

Sui

et al. 2018

The FEBS Journal

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Epigenetic regulation in cell senescence

et al. 2017

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Cell senescence, which is an irreversible state of cell proliferative arrest, has emerged as a potentially important contributor to tissue dysfunction and organismal ageing. Cell senescence is triggered by a variety of senescence stressors, which affect gene expression and multiple signalling pathways that give rise to various senescence phenotypes. Epigenetic mechanisms, as critical regulators of chromosomal architecture and gene expression, have added an extra dimension to the molecular mechanisms of cell senescence. Cell senescence is accompanied by changes in DNA methylation, histone-associated epigenetic processes, chromatin remodelling and ncRNA expression. Those senescence-associated epigenetic alterations interact with the senescence regulatory programme networks and lead to various cell senescence phenotypes. This review provides a comprehensive overview of epigenetic changes and their effects on cell senescence. The differences in epigenetic alterations among different types of senescence are also discussed. Furthermore, we summarise the interactions among different epigenetic mechanisms during cell senescence and analyse the possibility of using epigenetic signatures as biomarkers and therapeutic targets for the treatment of senescence-associated diseases.

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Human INO80/YY1 chromatin remodeling complex transcriptionally regulates the BRCA2- and CDKN1A-interacting protein (BCCIP) in cells

Sui

Ding

et al. 2016

Protein Cell

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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.

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Negative Regulation of p21Waf1/Cip1 by Human INO80 Chromatin Remodeling Complex Is Implicated in Cell Cycle Phase G2/M Arrest and Abnormal Chromosome Stability

Cited by 20 publications

References 45 publications

The chromatin remodeling protein INO80 contributes to the removal of H2A.Z at the p53‐binding site of the p21 gene in response to doxorubicin

The chromatin remodeling protein INO80 contributes to the removal of H2A.Z at the p53‐binding site of the p21 gene in response to doxorubicin

Epigenetic regulation in cell senescence

Human INO80/YY1 chromatin remodeling complex transcriptionally regulates the BRCA2- and CDKN1A-interacting protein (BCCIP) in cells

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