ETS1 and SP1 drive DHX15 expression in acute lymphoblastic leukaemia.

ETS1 and SP1 drive DHX15 expression in acute lymphoblastic leukaemia.
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ETS1和SP1在急性淋巴细胞白血病中驱动DHX15表达

DOI:
10.1111/jcmm.13525
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发表时间:
2018-05
影响因子:
5.3
通讯作者:
Wang SY
Wang SY
中科院分区:
医学2区
文献类型:
--
作者:
Chen XL;Cai YH;Liu Q;Pan LL;Shi SL;Liu XL;Chen Y;Li JG;Wang J;Li Y;Li XF;Wang SY

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DHX 15在白血病发生和白血病复发中起作用。然而,DHX 15在ALL中的转录调控机制尚未阐明。本研究的目的是探索DHX 15基因启动子区的功能,并研究调控该基因转录的转录因子。用几种截短的构建体进行的荧光素酶测定鉴定出501-bp区域为DHX 15的核心启动子区。定点突变、电泳迁移率改变和染色质免疫沉淀分析表明,ETS 1和SP1占据DHX 15启动子。此外,ETS 1和SP1的敲低导致DHX 15的抑制,而这些基因的过表达导致DHX 15的上调。有趣的是,在诊断时从ALL患者获得的样本中,ETS 1和SP1均与DHX 15表达呈正相关。此外,在患者和对照组之间没有观察到DHX 15核心启动子区域甲基化的差异。总之,我们确定了DHX 15的核心启动子区域,并证明ETS 1和SP1调节ALL中DHX 15的表达。
DHX15 plays a role in leukaemogenesis and leukaemia relapse. However, the mechanism underlying the transcriptional regulation of DHX15 in ALL has not been elucidated. Our present study aimed to explore the functional promoter region of DHX15 and to investigate the transcription factors controlling the transcription of this gene. A luciferase assay performed with several truncated constructs identified a 501‐bp region as the core promoter region of DHX15. Site‐directed mutagenesis, electrophoretic mobility shift and chromatin immunoprecipitation assays showed that ETS1 and SP1 occupied the DHX15 promoter. Furthermore, knockdown of ETS1 and SP1 resulted in suppression of DHX15, whereas the overexpression of these genes led to up‐regulation of DHX15. Interestingly, in samples obtained from patients with ALL at diagnosis, both ETS1 and SP1 correlated positively with DHX15 expression. Additionally, differences in methylation of the DHX15 core promoter region were not observed between the patients and controls. In conclusion, we identified the core promoter region of DHX15 and demonstrated that ETS1 and SP1 regulated DHX15 expression in ALL.
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