RE1 silencing transcription factor (REST) negatively regulates ALL1-fused from chromosome 1q (AF1q) gene transcription.
RE1 silencing transcription factor (REST) negatively regulates ALL1-fused from chromosome 1q (AF1q) gene transcription.
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RE1 沉默转录因子 (REST) 负向调节来自染色体 1q (AF1q) 的 ALL1 融合基因转录。
DOI：
10.1186/s12867-015-0043-7
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发表时间：
2015-09-05
影响因子：
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通讯作者：
Sun X
中科院分区：
文献类型：
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作者：
Hu Y;Sun Q;Zhang C;Sha Q;Sun X
ALL 1-fused from chromosome 1 q（AF 1 q）最初被认为是一种致癌因子，与神经元发育有关，但其上游调控机制尚不清楚。我们的研究表明，REST（RE 1 silencing transcription factor，RE 1沉默转录因子）是神经发育的关键转录因子，它可以下调AF 1 q基因的表达。启动子检测在人AF 1 q启动子的−383至−363 bp处鉴定出一个神经元限制性沉默元件。电泳迁移率变动分析（EMSA）和染色质免疫沉淀（CHIP）证实REST与AF 1 q基因启动子的NRSE结合。此外，小鼠神经发育过程中Af 1 q与Rest表达水平的负相关性支持了REST对AF 1 q的负调节作用以及AF 1 q在神经发育中的潜在功能。这些结果表明，REST通过直接结合AF 1 q启动子−383至−363 bp处的NRSE来调节AF 1 q基因转录。
ALL1-fused from chromosome 1q (AF1q), originally considered as an oncogenic factor, has been implicated in neuronal development; however, its upstream regulatory mechanisms in neural system remained elusive. Our study showed that REST (RE1 silencing transcription factor), a key transcription factor in neurodevelopment, could down-regulate the gene expression of AF1q. The promoter assay identified a neuron-restrictive silencer element at −383 to −363 bp of human AF1q promoter. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (CHIP) confirmed the binding of REST to the NRSE in AF1q gene promoter. Additionally, the negative correlation between the expression levels of Af1q and Rest in mice neurodevelopment supported the negative regulation of AF1q by REST and the potential functions of AF1q in neurodevelopment. These results demonstrate that REST regulates AF1q gene transcription through directly binding to a NRSE at −383 to −363 bp of AF1q promoter.