Stereotyped p53 binding tuned by chromatin accessibility

We accessed the cell type specificity of p53 by directly measuring DNA binding in twelve cell lines in response to ionizing radiation. We find that that vast majority of binding sites are occupied across all cells lines uniformly, in contrast to p53 regulated gene expression which shows great diversity in the same context. We further identify a subset of p53 binding sites that are more restricted, appearing in one or a few cell lines. We find that chromatin accessibility explains much of these differential binding events. Overall design: p53 DNA binding was measured in twelve cell lines after IR by ChIPseq. The transcriptional response of each of the twelve lines was also measured by mRNAseq. To explore the influence of chromatin accessability p53 binding was compared to ATAC-seq data from two cell lines.

本研究通过直接检测12种细胞系在电离辐射（ionizing radiation）刺激下的p53 DNA结合情况，阐明了p53的细胞类型特异性调控特征。研究发现，绝大多数p53结合位点在所有细胞系中均呈现一致的结合态势；与之形成鲜明对比的是，在相同处理背景下，p53调控的基因表达却表现出显著的异质性。本研究进一步鉴定出一类具有结合限制性的p53结合位点亚群，这类位点仅在1种或少数几种细胞系中出现结合信号。研究表明，染色质开放性（chromatin accessibility）可解释大部分此类差异结合事件。
实验设计概况：本研究通过ChIP测序（ChIPseq）检测了12种细胞系经IR（电离辐射）处理后的p53 DNA结合水平；同时通过mRNA测序（mRNAseq）测定了这12种细胞系各自的转录应答情况。为探究染色质开放性对p53结合的调控作用，本研究将p53结合数据与2种细胞系的ATAC测序（ATAC-seq）数据进行了对比分析。