Integrative genomic analysis reveals widespread enhancer regulation by p53 in response to DNA damage.
Integrative genomic analysis reveals widespread enhancer regulation by p53 in response to DNA damage.
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综合基因组分析揭示了p53对DNA损伤的广泛调节。
DOI：
10.1093/nar/gkv284
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发表时间：
2015-05-19
影响因子：
14.9
通讯作者：
Rinn JL
中科院分区：
文献类型：
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作者：
Younger ST;Kenzelmann-Broz D;Jung H;Attardi LD;Rinn JL
肿瘤抑制基因p53作为蛋白质编码基因的直接转录激活因子已被广泛研究。然而，最近的研究揭示了基因组非编码区内p53的新调控功能。在这里，我们使用一个系统的方法，整合转录组范围内的表达分析，全基因组p53结合概况和染色质状态图，以表征的全球调节作用的p53在DNA损伤。值得注意的是，我们的方法在人和小鼠原代成纤维细胞模型中鉴定了p53网络的保守特征。除了已知的p53靶点外，我们还鉴定了许多以前未被认识的mRNA和长的非编码RNA，它们受p53的调控。此外，我们发现p53结合主要发生在人和小鼠模型系统的增强子内。调节增强子活性的能力为p53网络提供了额外的复杂性，并极大地扩展了由p53直接调控的基因组元件的多样性。
The tumor suppressor p53 has been studied extensively as a direct transcriptional activator of protein-coding genes. Recent studies, however, have shed light on novel regulatory functions of p53 within noncoding regions of the genome. Here, we use a systematic approach that integrates transcriptome-wide expression analysis, genome-wide p53 binding profiles and chromatin state maps to characterize the global regulatory roles of p53 in response to DNA damage. Notably, our approach identified conserved features of the p53 network in both human and mouse primary fibroblast models. In addition to known p53 targets, we identify many previously unappreciated mRNAs and long noncoding RNAs that are regulated by p53. Moreover, we find that p53 binding occurs predominantly within enhancers in both human and mouse model systems. The ability to modulate enhancer activity offers an additional layer of complexity to the p53 network and greatly expands the diversity of genomic elements directly regulated by p53.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
64.5
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
通讯作者：
Rinn JL
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
64.8
作者：
Gong, Chenguang;Maquat, Lynne E.
通讯作者：
Maquat, Lynne E.