BACKGROUND The tumor suppressor p53 is a major regulator of the DNA damage response and has been suggested to selectively bind and activate cell-type specific gene expression programs. However recent studies and meta-analyses of genomic data propose largely uniform, and condition independent p53 binding and thus question the selective and cell-type dependent function of p53. RESULTS To systematically assess the cell-type specificity of p53, we measured its association with DNA in 12 p53 wild-type cancer cell lines, from a range of epithelial linages, in response to ionizing radiation. We found that the majority of bound sites were occupied across all cell lines, however we also identified a subset of binding sites that were specific to one or a few cell lines. Unlike the shared p53-bound genome, which was not dependent on chromatin accessibility, the association of p53 with these atypical binding sites was well explained by chromatin accessibility and could be modulated by forcing cell state changes such as the epithelial-to-mesenchymal transition. CONCLUSIONS Our study reconciles previous conflicting views in the p53 field, by demonstrating that although the majority of p53 DNA binding is conserved across cell types, there is a small set of cell line specific binding sites that depend on cell state.

中文翻译：

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鉴定通用和细胞型特异性p53 DNA结合。

背景技术肿瘤抑制因子p53是DNA损伤反应的主要调节剂，并被认为可以选择性结合并激活细胞型特异性基因表达程序。然而，最近的研究和基因组数据的荟萃分析提出了很大程度上统一且不受条件影响的p53结合，因此对p53的选择性和细胞类型依赖性功能提出了质疑。结果为了系统地评估p53的细胞类型特异性，我们测量了12种p53野生型癌细胞系中p53与DNA的关系，这些细胞系来自一系列上皮细胞，响应电离辐射。我们发现大多数结合位点都占据了所有细胞系，但是我们还发现了一个或几个细胞系特异的结合位点的子集。与不依赖染色质可及性的共享p53结合基因组不同，染色质的可及性很好地解释了p53与这些非典型结合位点之间的联系，并且可以通过强迫细胞状态变化（例如上皮到间质转化）来调节p53。结论我们的研究通过证明尽管大多数p53 DNA结合在不同细胞类型之间均得到保守，但仍有少数细胞系特异性结合位点取决于细胞状态，从而调和了先前在p53领域相互矛盾的观点。