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生长信号利用CGGBP1抑制Alu短散在核元件的转录。

Growth signals employ CGGBP1 to suppress transcription of Alu-SINEs.

作者信息

Agarwal Prasoon, Enroth Stefan, Teichmann Martin, Jernberg Wiklund Helena, Smit Arian, Westermark Bengt, Singh Umashankar

机构信息

a Department of Immunology, Genetics and Pathology, Rudbeck Laboratory , Uppsala University , Uppsala , Sweden.

b University of Bordeaux, IECB , ARNA laboratory, Equipe Labellisée Contre le Cancer , Pessac , France.

出版信息

Cell Cycle. 2016 Jun 17;15(12):1558-71. doi: 10.4161/15384101.2014.967094.

Abstract

CGGBP1 (CGG triplet repeat-binding protein 1) regulates cell proliferation, stress response, cytokinesis, telomeric integrity and transcription. It could affect these processes by modulating target gene expression under different conditions. Identification of CGGBP1-target genes and their regulation could reveal how a transcription regulator affects such diverse cellular processes. Here we describe the mechanisms of differential gene expression regulation by CGGBP1 in quiescent or growing cells. By studying global gene expression patterns and genome-wide DNA-binding patterns of CGGBP1, we show that a possible mechanism through which it affects the expression of RNA Pol II-transcribed genes in trans depends on Alu RNA. We also show that it regulates Alu transcription in cis by binding to Alu promoter. Our results also indicate that potential phosphorylation of CGGBP1 upon growth stimulation facilitates its nuclear retention, Alu-binding and dislodging of RNA Pol III therefrom. These findings provide insights into how Alu transcription is regulated in response to growth signals.

摘要

CGGBP1(CGG三联体重复结合蛋白1)调控细胞增殖、应激反应、胞质分裂、端粒完整性和转录。它可以通过在不同条件下调节靶基因表达来影响这些过程。鉴定CGGBP1靶基因及其调控机制可以揭示转录调节因子如何影响如此多样的细胞过程。在这里,我们描述了CGGBP1在静止或生长细胞中差异基因表达调控的机制。通过研究CGGBP1的全局基因表达模式和全基因组DNA结合模式,我们表明它以反式影响RNA聚合酶II转录基因表达的一种可能机制依赖于Alu RNA。我们还表明它通过结合Alu启动子顺式调控Alu转录。我们的结果还表明,生长刺激后CGGBP1的潜在磷酸化促进其核内保留、Alu结合以及RNA聚合酶III从其上解离。这些发现为响应生长信号时Alu转录如何被调控提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10dc/4934077/f2f3a99e9391/kccy-15-12-967094-g001.jpg

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