Modulation of gene expression via overlapping binding sites exerted by ZNF143, Notch1 and THAP11.
Modulation of gene expression via overlapping binding sites exerted by ZNF143, Notch1 and THAP11.
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DOI：
10.1093/nar/gkt088
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发表时间：
2013-04
影响因子：
14.9
通讯作者：
Carbon P
中科院分区：
文献类型：
--
作者：
Ngondo-Mbongo RP;Myslinski E;Aster JC;Carbon P
ZNF143是一种锌指蛋白，参与聚合酶II和III启动子的编码和非编码基因的转录调控。我们的研究破译了ZNF143与两个以前不相关的转录因子Notch1/ICN1和乙醇相关蛋白11(THAP11)在几个人和小鼠细胞中的全基因组调控作用。我们发现在>；3000基因的启动子中有两个不同的基序SBS1和SBS2与ZNF143结合事件相关。在没有共占的情况下，这些位点还与T淋巴母细胞白血病细胞中的Notch1/ICN1以及THAP11结合，THAP11是一种参与胚胎干细胞自我更新的因子。我们提供的证据表明，ICN1结合与ZNF143结合事件在SBS1和SBS2基序上重叠，而重叠仅在THAP11的SBS2上发生。我们证明，这三个因子通过相互排斥地占据重叠的结合位点来调节共同的靶基因的表达。我们提出的模型预测，这三个因素之间的结合竞争控制着生物过程，如肿瘤细胞和干细胞的快速细胞生长。总体而言，我们的研究建立了ZNF143、THAP11和ICN1之间的新关系，并揭示了ZNF143介导的基因调控的重要见解。
ZNF143 is a zinc-finger protein involved in the transcriptional regulation of both coding and non-coding genes from polymerase II and III promoters. Our study deciphers the genome-wide regulatory role of ZNF143 in relation with the two previously unrelated transcription factors Notch1/ICN1 and thanatos-associated protein 11 (THAP11) in several human and murine cells. We show that two distinct motifs, SBS1 and SBS2, are associated to ZNF143-binding events in promoters of >3000 genes. Without co-occupation, these sites are also bound by Notch1/ICN1 in T-lymphoblastic leukaemia cells as well as by THAP11, a factor involved in self-renewal of embryonic stem cells. We present evidence that ICN1 binding overlaps with ZNF143 binding events at the SBS1 and SBS2 motifs, whereas the overlap occurs only at SBS2 for THAP11. We demonstrate that the three factors modulate expression of common target genes through the mutually exclusive occupation of overlapping binding sites. The model we propose predicts that the binding competition between the three factors controls biological processes such as rapid cell growth of both neoplastic and stem cells. Overall, our study establishes a novel relationship between ZNF143, THAP11 and ICN1 and reveals important insights into ZNF143-mediated gene regulation.
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影响因子：
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作者：
Halbig KM;Lekven AC;Kunkel GR
通讯作者：
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作者：
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影响因子：
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作者：
Anno YN;Myslinski E;Ngondo-Mbongo RP;Krol A;Poch O;Lecompte O;Carbon P
通讯作者：
Carbon P
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影响因子：
14.9
作者：
Gérard MA;Myslinski E;Chylak N;Baudrey S;Krol A;Carbon P
通讯作者：
Carbon P