Characterization of genome-wide p53-binding sites upon stress response.
Characterization of genome-wide p53-binding sites upon stress response.
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DOI：
10.1093/nar/gkn232
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发表时间：
2008-06
影响因子：
14.9
通讯作者：
Lohrum M
中科院分区：
文献类型：
--
作者：
Smeenk L;van Heeringen SJ;Koeppel M;van Driel MA;Bartels SJ;Akkers RC;Denissov S;Stunnenberg HG;Lohrum M
抑癌基因p53是一种序列特异性转录因子，调控参与不同应激反应的靶基因的表达。要了解p53的基本转录功能，其DNA结合库的公正分析是至关重要的。在全基因组平铺芯片上芯片的方法中，我们已经确定并表征了放线菌素D治疗后p53的1546个结合位点。在这些结合位点中，已知的还有新的p53靶位点，其中包括潜在的新转录物的调控区。使用这个收集的全基因组结合位点，一个新的高置信度的算法，p53scan，以确定p53共识结合基序。引人注目的是，该基序存在于所有结合序列的大多数中，其中83%的所有结合位点含有该基序。在结合位点的周围序列中，识别出了几个潜在调节辅结合物的基序。最后，我们发现，大多数的全基因组p53靶位点也可以结合过表达的p63和p73在体内，这表明他们可能在p53结合位点发挥重要作用。这强调了p53及其家族成员在靶基因结合的背景下可能的相互作用。我们的研究极大地扩展了已知的，实验验证的p53结合位点库，并为未来的研究提供了有价值的知识基础。
The tumor suppressor p53 is a sequence-specific transcription factor, which regulates the expression of target genes involved in different stress responses. To understand p53's essential transcriptional functions, unbiased analysis of its DNA-binding repertoire is pivotal. In a genome-wide tiling ChIP-on-chip approach, we have identified and characterized 1546 binding sites of p53 upon Actinomycin D treatment. Among those binding sites were known as well as novel p53 target sites, which included regulatory regions of potentially novel transcripts. Using this collection of genome-wide binding sites, a new high-confidence algorithm was developed, p53scan, to identify the p53 consensus-binding motif. Strikingly, this motif was present in the majority of all bound sequences with 83% of all binding sites containing the motif. In the surrounding sequences of the binding sites, several motifs for potential regulatory cobinders were identified. Finally, we show that the majority of the genome-wide p53 target sites can also be bound by overexpressed p63 and p73 in vivo, suggesting that they can possibly play an important role at p53 binding sites. This emphasizes the possible interplay of p53 and its family members in the context of target gene binding. Our study greatly expands the known, experimentally validated p53 binding site repertoire and serves as a valuable knowledgebase for future research.
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影响因子：
64.5
作者：
Cawley, S;Bekiranov, S;Gingeras, TR
通讯作者：
Gingeras, TR
影响因子：
14.5
作者：
El-Deiry, WS
通讯作者：
El-Deiry, WS
影响因子：
14.9
作者：
通讯作者：
--
影响因子：
64.5
作者：
Avantaggiati, ML;Ogryzko, V;Kelly, K
通讯作者：
Kelly, K
影响因子：
5.8
作者：
Al-Shahrour, F;Díaz-Uriarte, R;Dopazo, J
通讯作者：
Dopazo, J