YY1/BCCIP Coordinately Regulates P53-Responsive Element (p53RE)-Mediated Transactivation of p21Waf1/Cip1

Abstract

Transactivation of p21 (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 p21 promoter and negatively regulates p21. As one of the key subunits of the INO80 complex, YY1 has also been confirmed to bind to the p53RE sites of p21 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 p21. Here we present evidence that the YY1/BCCIP complex coordinatively regulates p53RE-mediated p21 transactivation. We first confirmed the cross-interaction between YY1, BCCIP, and p53, suggesting an intrinsic link between three proteins in the regulation of p21 transcription. In dual luciferase assays, YY1 inhibited p53RE-mediated luciferase activity, whereas BCCIP revealed the opposite effect. More interestingly, the region 146–270 amino acids of YY1, which bound to BCCIP, increased p53-mediated luciferase activity, indicating the complexity of the YY1/BCCIP complex in co-regulating p21 transcription. Further in-depth research confirmed the co-occupancy of YY1/BCCIP with p53 at the p53RE-proximal region of p21. Lentiviral-mediated knockdown of BCCIP inhibited the recruitment of p53 and YY1 at the p53RE proximal region of p21; however, this phenomenon was reversed by expressing exogenous YY1, suggesting the collaborative regulation of YY1/BCCIP complex in p53RE-mediated p21 transcription. These data provide new insights into the transcriptional regulation of p21 by the YY1/BCCIP complex.

ΔNp63α facilitates proliferation and migration, and modulates the chromatin landscape in intrahepatic cholangiocarcinoma cells

“…Therefore, we speculated whether YY1 also plays a role in p63-regulated enhancer–promoter interactions. It has already been shown that YY1 binds to the p53 protein [ 52 ], and p63 is a conserved homologue of p53; therefore, we investigated whether p63 can also interact with YY1. We conducted co-immunoprecipitation (Co-IP) experiments on the RBE_vector vs. RBE_over groups, and found that p63 and YY1 can bind to each other (Fig.…”

Mutational Damages in Malignant Lung Tumors

“…Recent studies by several authors (Ding, 2018;Sui, 2019;Meliala, 2020; showed that the transactivation of p21 (cyclin-dependent kinase inhibitor 1A) 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 the p21 promoter and negatively regulates p21 (Ding, 2018).…”

Studies on the Role of the Transcription Factor Tcf21 in the Transdifferentiation of Parietal Epithelial Cells into Podocyte-Like Cells

“…Since it was reported that the transcription factor YY1 is an negative regulator of p53 as well as of p21 [60][61][62][63][64], another important protein for cell cycle regulation and that the loss of YY1 resulted in polyploidy and chromatid aberrations [65], we wanted to know whether we could rescue the Tcf21-induced MBM by the co-expression of YY1. Indeed, we observed a complete rescue of the MBM suggesting a role of YY1 in the differentiation of podocytes.…”