YY1/BCCIP Coordinately Regulates P53-Responsive Element (p53RE)-Mediated Transactivation of p21^Waf1/Cip1

• Main Authors: Yi Sui, Tingting Wu, Fuqiang Li, Fei Wang, Yong Cai, Jingji Jin
• Format: Article
• Language: English
• Published: MDPI AG 2019-04-01
• Series: International Journal of Molecular Sciences
• Subjects: transactivation; gene transcription; p53; BCCIP; <i>p21</i>; YY1
• Online Access: https://www.mdpi.com/1422-0067/20/9/2095

Transactivation of <i>p21</i> (cyclin-dependent kinase inhibitor 1A, CDKN1A) is closely related to the recruitment of transcription cofactors at the p53 responsive elements (p53REs) in its promoter region. Human chromatin remodeling enzyme INO80 can be recruited to the p53REs of <i>p21</i> promoter and negatively regulates <i>p21</i>. As one of the key subunits of the INO80 complex, YY1 has also been confirmed to bind to the p53RE sites of <i>p21</i> promoter. Importantly, YY1 was recently reported to be bound and stabilized by BCCIP (BRCA2 and CDKN1A-interacting protein). Therefore, we hypothesized that the YY1/BCCIP complex plays an important role in regulating the transactivation of <i>p21</i>. Here we present evidence that the YY1/BCCIP complex coordinatively regulates p53RE-mediated <i>p21</i> transactivation. We first confirmed the cross-interaction between YY1, BCCIP, and p53, suggesting an intrinsic link between three proteins in the regulation of <i>p21</i> transcription. In dual luciferase assays, YY1 inhibited p53RE-mediated luciferase activity, whereas BCCIP revealed the opposite effect. More interestingly, the region 146&#8722;270 amino acids of YY1, which bound to BCCIP, increased p53-mediated luciferase activity, indicating the complexity of the YY1/BCCIP complex in co-regulating <i>p21</i> transcription. Further in-depth research confirmed the co-occupancy of YY1/BCCIP with p53 at the p53RE-proximal region of <i>p21</i>. Lentiviral-mediated knockdown of BCCIP inhibited the recruitment of p53 and YY1 at the p53RE proximal region of <i>p21</i>; however, this phenomenon was reversed by expressing exogenous YY1, suggesting the collaborative regulation of YY1/BCCIP complex in p53RE-mediated <i>p21</i> transcription. These data provide new insights into the transcriptional regulation of <i>p21</i> by the YY1/BCCIP complex.