The oncogenic EWS-FLI1 protein binds in vivo GGAA microsatellite sequences with potential transcriptional activation function.
The oncogenic EWS-FLI1 protein binds in vivo GGAA microsatellite sequences with potential transcriptional activation function.
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致癌EWS-FLI1蛋白在体内GGAA微卫星序列结合了潜在的转录激活函数。
DOI：
10.1371/journal.pone.0004932
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Delattre O
中科院分区：
文献类型：
--
作者：
Guillon N;Tirode F;Boeva V;Zynovyev A;Barillot E;Delattre O
EWS和ETS家族成员之间的融合是尤文瘤中的关键致癌事件，并且已经鉴定了重要的EWS-FLI 1靶基因。然而，到目前为止，对EWS-FLI 1靶点的研究仅限于启动子区域，尚未对体内EWS-FLI 1结合位点进行全基因组综合分析。使用ChIP-Seq的方法来调查EWS-FLI 1结合的DNA序列在两个尤文细胞系中，我们表明，这种嵌合转录因子优先结合两种类型的序列，包括共识ETS基序和微卫星序列。大多数结合位点位于启动子区域之外。含有超过9个GGAA重复序列的微卫星在EWS-FLI 1免疫沉淀物中非常显著富集。此外，在报告基因实验中，转录激活高度依赖于构建体中包含的重复序列的数量。重要的是，体内EWS-FLI 1结合的微卫星与EWS-FLI 1驱动的基因激活显著相关。总而言之，这些结果指出了微卫星元件对远距离转录调控和肿瘤发生的可能贡献。
The fusion between EWS and ETS family members is a key oncogenic event in Ewing tumors and important EWS-FLI1 target genes have been identified. However, until now, the search for EWS-FLI1 targets has been limited to promoter regions and no genome-wide comprehensive analysis of in vivo EWS-FLI1 binding sites has been undertaken. Using a ChIP-Seq approach to investigate EWS-FLI1-bound DNA sequences in two Ewing cell lines, we show that this chimeric transcription factor preferentially binds two types of sequences including consensus ETS motifs and microsatellite sequences. Most bound sites are found outside promoter regions. Microsatellites containing more than 9 GGAA repeats are very significantly enriched in EWS-FLI1 immunoprecipitates. Moreover, in reporter gene experiments, the transcription activation is highly dependent upon the number of repeats that are included in the construct. Importantly, in vivo EWS-FLI1-bound microsatellites are significantly associated with EWS-FLI1-driven gene activation. Put together, these results point out the likely contribution of microsatellite elements to long-distance transcription regulation and to oncogenesis.
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影响因子：
14.9
作者：
Jothi, Raja;Cuddapah, Suresh;Barski, Artem;Cui, Kairong;Zhao, Keji
通讯作者：
Zhao, Keji
影响因子：
5.3
作者：
Kim, S;Denny, CT;Wisdom, R
通讯作者：
Wisdom, R
DOI：
10.1073/pnas.0801073105
发表时间：
2008-07-22
影响因子：
11.1
作者：
Gangwal, Kunal;Sankar, Savita;Lessnick, Stephen L.
通讯作者：
Lessnick, Stephen L.
影响因子：
10.5
作者：
Hollenhorst, Peter C.;Shah, Atul A.;Graves, Barbara J.
通讯作者：
Graves, Barbara J.
影响因子：
7
作者：
Blanchette, M;Bataille, AR;Robert, FO
通讯作者：
Robert, FO