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首页> 外文期刊>Cell cycle >Distinct p53 genomic binding patterns in normal and cancer-derived human cells.
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Distinct p53 genomic binding patterns in normal and cancer-derived human cells.

机译：正常和癌症来源的人类细胞中明显的p53基因组结合模式。

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摘要

We report here genome-wide analysis of the tumor suppressor p53 binding sites in normal human cells. 743 high-confidence ChIP-seq peaks representing putative genomic binding sites were identified in normal IMR90 fibroblasts using a reference chromatin sample. More than 40% were located within 2 kb of a transcription start site (TSS), a distribution similar to that documented for individually studied, functional p53 binding sites and, to date, not observed by previous p53 genome-wide studies. Nearly half of the high-confidence binding sites in the IMR90 cells reside in CpG islands, in marked contrast to sites reported in cancer-derived cells. The distinct genomic features of the IMR90 binding sites do not reflect a distinct preference for specific sequences, since the de novo developed p53 motif based on our study is similar to those reported by genome-wide studies of cancer cells. More likely, the different chromatin landscape in normal, compared with cancer-derived cells, influences p53 binding via modulating availability of the sites. We compared the IMR90 ChIPseq peaks to the recently published IMR90 methylome and demonstrated that they are enriched at hypomethylated DNA. Our study represents the first genome-wide, de novo mapping of p53 binding sites in normal human cells and reveals that p53 binding sites reside in distinct genomic landscapes in normal and cancer-derived human cells.
机译：我们在这里报告了正常人细胞中肿瘤抑制因子p53结合位点的全基因组分析。使用参考染色质样品，在正常IMR90成纤维细胞中鉴定出代表假定的基因组结合位点的743个高可信度ChIP-seq峰。超过40％的位点位于转录起始位点（TSS）的2 kb之内，其分布与单独研究的功能性p53结合位点记录的相似，迄今为止，以前的p53基因组范围的研究均未观察到。 IMR90细胞中近一半的高可信度结合位点位于CpG岛中，这与癌症衍生细胞中报道的位点形成鲜明对比。 IMR90结合位点的独特基因组特征并未反映出对特定序列的独特偏好，因为根据我们的研究从头开发的p53基序与癌细胞的全基因组研究所报道的相似。与癌症衍生细胞相比，正常情况下不同的染色质分布可能通过调节位点的可用性影响p53结合。我们将IMR90 ChIPseq峰与最近发布的IMR90甲基化组进行了比较，并证明它们在次甲基化DNA处富集。我们的研究代表了正常人细胞中p53结合位点的首个全基因组从头作图，并揭示了p53结合位点位于正常人和癌症来源的人细胞中不同的基因组格局中。

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