Abstract:Abstract: Previous studies have shown that p53 can participate in enhancer regulation and affect chromo-some accessibility. However, the feature of p53-regulated enhancers as well as the regulatory network formed by p53 and enhancers in breast cancer are unclear. To this end, multiple omics data were integrated and 459 p53-bound enhancers (Enhp53) were identified in MCF-7 cells. By comparison of their characteristics, it was found that Enhp53 expression and H3K4me1, H3K4me2, H3K4me3, H3K9ac, and H3K27ac signals were significantly higher than those of p53-unbound enhancers (Enhno-p53). By analyzing the ChIP-seq data of 76 tran-scription factors, 36 transcription factors, such as GATA3, FOXA1, and DPF2, were found to co-regulate enhancers with p53. By analyzing the RNA-seq data before and after activation by Nutlin in MCF-7 cells, a total of 148 Enhp53-mRNAs were identified at both proximal and distal regulatory levels, among which FOS was regulated by two enhancers and affected the overall survival time of breast cancer patients significantly. Functional enrichment analysis found that Enhp53 target genes were enriched in DNA damage, apoptosis, and p53-mediated tumor signaling pathways significantly. The above results indicate that Enhp53 is different from Enhno-p53, and p53 binds to Enhp53 by cooperating with other transcription factors and then participates in biological processes and signaling pathways in breast cancer.
引用本文:
张 茵, 王文著, 谭政堂, 李昶蓥, 岳俊杰, 郭志云. 乳腺癌中p53调控增强子的特征与功能分析[J]. 生命科学研究, 2020, 24(6): 476-483. ZHANG Yin, WANG Wen-zhu, TAN Zheng-tang, LI Chang-ying, YUE Jun-jie, GUO Zhi-yun. Characteristics and Functional Analysis of p53-regulated Enhancers in Breast Cancer. Life Science Research, 2020, 24(6): 476-483.