Role of CTCF in Regulating SLC45A3-ELK4 Chimeric RNA.
Role of CTCF in Regulating SLC45A3-ELK4 Chimeric RNA.
复制标题
CTCF在调节SLC45A3-ELK4嵌合RNA中的作用。
DOI：
10.1371/journal.pone.0150382
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Qin F;Song Y;Zhang Y;Facemire L;Frierson H;Li H
嵌合RNA SLC 45 A3-ELK 4是两个相邻基因之间顺式剪接的产物（cis-SAGe）。尽管SLC 45 A3-ELK 4具有生物学和临床意义，但其产生机制尚未阐明。在一个细胞系中显示，转录因子CTCF与位于基因边界处或附近的绝缘子的结合与嵌合体的水平负相关。为了研究这种顺式SAGe事件的机制，我们对可能在这种转录通读中发挥作用的潜在区域进行了测序。我们不能检测到突变的转录终止位点，绝缘子网站，剪接位点，或CTCF本身在LNCaP细胞，从而表明一个“软连线”的机制，在调节顺式SAGe事件。为了研究CTCF在调节嵌合RNA表达中的作用，我们比较了CTCF与不同细胞系以及临床样品中绝缘子的结合水平。令人惊讶的是，我们没有发现CTCF水平或其与绝缘子的结合与不同样品中的SLC 45 A3-ELK 4表达之间的负相关性。然而，在三种前列腺癌细胞系中，不同的环境因素可导致嵌合RNA的表达水平发生变化，并且这些变化确实与CTCF水平和/或其与绝缘子的结合呈负相关。因此，我们得出结论，CTCF及其与绝缘体的结合不是不同细胞系或临床病例中差异SLC 45 A3-ELK 4表达的主要原因。然而，它们可能是相同细胞响应不同环境信号的机制，以调节SLC 45 A3-ELK 4嵌合RNA的表达。这种对不同环境线索的反应对于其他顺式SAGe事件并不普遍，因为我们在16种新鉴定的嵌合RNA中仅发现一种显示出与SLC 45 A3-ELK 4相似的模式。
The chimeric RNA, SLC45A3-ELK4, was found to be a product of cis-splicing between the two adjacent genes (cis-SAGe). Despite the biological and clinical significance of SLC45A3-ELK4, its generating mechanism has not been elucidated. It was shown in one cell line that the binding of transcription factor CTCF to the insulators located at or near the gene boundaries, inversely correlates with the level of the chimera. To investigate the mechanism of such cis-SAGe events, we sequenced potential regions that may play a role in such transcriptional read-through. We could not detect mutations at the transcription termination site, insulator sites, splicing sites, or within CTCF itself in LNCaP cells, thus suggesting a “soft-wired” mechanism in regulating the cis-SAGe event. To investigate the role CTCF plays in regulating the chimeric RNA expression, we compared the levels of CTCF binding to the insulators in different cell lines, as well as clinical samples. Surprisingly, we did not find an inverse correlation between CTCF level, or its bindings to the insulators and SLC45A3-ELK4 expression among different samples. However, in three prostate cancer cell lines, different environmental factors can cause the expression levels of the chimeric RNA to change, and these changes do inversely correlate with CTCF level, and/or its bindings to the insulators. We thus conclude that CTCF and its bindings to the insulators are not the primary reasons for differential SLC45A3-ELK4 expression in different cell lines, or clinical cases. However, they are the likely mechanism for the same cells to respond to different environmental cues, in order to regulate the expression of SLC45A3-ELK4 chimeric RNA. This response to different environmental cues is not general to other cis-SAGe events, as we only found one out of 16 newly identified chimeric RNAs showing a pattern similar to SLC45A3-ELK4.