Abstract
We previously identified an ATP-dependent human Ino80 (INO80) chromatin remodeling complex which shares a set of core subunits with yeast Ino80 complex. Although research evidence has suggested that INO80 complex functions in gene transcription and genome stability, the precise mechanism remains unclear. Herein, based on gene expression profiles from the INO80 complex-knockdown in HeLa cells, we first demonstrate that INO80 complex negatively regulates the p21Waf1/Cip1 (p21) expression in a p53-mediated mechanism. In chromatin immunoprecipitation (ChIP) and a sequential ChIP (Re-ChIP) assays, we determined that the INO80 complex and p53 can bind to the same promoter region of p21 gene (-2.2kb and -1.0kb upstream of the p21 promoter region), and p53 is required for the recruitment of the INO80 complex to the p21 promoter. RNAi knockdown strategies of INO80 not only led to prolonged progression of cell cycle phase G2/M to G1, but it also resulted in abnormal chromosome stability. Interestingly, high expression of p21 was observed in most morphologically-changed cells, suggesting that negative regulation of p21 by INO80 complex might be implicated in maintaining the cell cycle process and chromosome stability. Together, our findings will provide a theoretical basis to further elucidate the cellular mechanisms of the INO80 complex.
Highlights
Ino80 chromatin remodeling complex, a member of Ino80 subfamily of the SWI/SNF chromatin remodeling superfamily, is highly conserved from Saccharomyces cerevisiae to human [1]
Increasing evidence suggests that INO80 chromatin remodeling complex plays a key role in gene transcriptional regulation [33, 34], the exact regulatory mechanisms are still unclear
In order to identify which potential target genes were regulated via knocking down the core components of the INO80 complexes, HeLa cells with specific siRNA transfections were sent to EMTD Science and Technology Development Co., Ltd. (Beijing, China) for gene expression profile analyses
Summary
A member of Ino subfamily of the SWI/SNF chromatin remodeling superfamily, is highly conserved from Saccharomyces cerevisiae to human [1]. We previously identified a human ATP-dependent chromatin remodeling complex, which shares eight core subunits with yeast Ino complex, including a SNF2 ATPase-INO80 catalytic subunit, actin-related proteins Arp, Arp and Arp, Tip49a and Tip49b AAA+ ATPases, PLOS ONE | DOI:10.1371/journal.pone.0137411. P21 Is Negatively Regulated by hIno Chromatin Remodeling Complex. Science and Technology Development Program (20130413002GH, YC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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