Computational identification of potential transcriptional regulators of TGF-β1 in human atherosclerotic arteries
Computational identification of potential transcriptional regulators of TGF-β1 in human atherosclerotic arteries
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DOI：
10.1016/j.ygeno.2014.05.001
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发表时间：
2014-05-01
期刊：
影响因子：
4.4
通讯作者：
Cerutti, Catherine
中科院分区：
文献类型：
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作者：
Dhaouadi, Nedra;Li, Jacques-Yuan;Cerutti, Catherine
TGF-β在动脉粥样硬化中是保护性的，但在转移性癌症中是有害的。我们的目的是确定在早期动脉粥样硬化中TGF-β的转录调控是否具有组织特异性。计算方法包括5个步骤：（i）从人类动脉粥样硬化颈动脉组织的微阵列数据中，鉴定与TGFB 1共表达最好的10个基因，（ii）选择11个邻近启动子，（iii）预测启动子共有的TFBS，（iv）鉴定与TGFB 1基因簇共表达的共同TF，和（v）将早期病变中的常见TF与晚期动脉粥样硬化病变和各种癌症中鉴定的TF进行比较。我们的研究结果表明，EGFR 1，SP1和KLF 6可能负责TGFB 1的基础表达，KLF 6出现特异性动脉粥样硬化病变。在与该基因簇共表达的转录因子中，转录激活因子（SLC 2A 4 RG、MAZ）和抑制因子（ZBTB 7A、PATZ 1、ZNF 263）可能参与了动脉粥样硬化中TGF β 1表达的微调。(C)2014 Elsevier Inc. All rights reserved.
TGF-beta is protective in atherosclerosis but deleterious in metastatic cancers. Our aim was to determine whether TGF-beta transcriptional regulation is tissue-specific in early atherosclerosis. The computational methods included 5 steps: (i) from microarray data of human atherosclerotic carotid tissue, to identify the 10 best co-expressed genes with TGFB1 (TGFB1 gene cluster), (ii) to choose the 11 proximal promoters, (iii) to predict the TFBS shared by the promoters, (iv) to identify the common TFs co-expressed with the TGFB1 gene cluster, and (v) to compare the common TFs in the early lesions to those identified in advanced atherosclerotic lesions and in various cancers. Our results show that EGR1, SP1 and KLF6 could be responsible for TGFB1 basal expression, KLF6 appearing specific to atherosclerotic lesions. Among the TFs co-expressed with the gene cluster, transcriptional activators (SLC2A4RG, MAZ) and repressors (ZBTB7A, PATZ1, ZNF263) could be involved in the fine-tuning of TGFB1 expression in atherosclerosis. (C) 2014 Elsevier Inc. All rights reserved.