OBJECTIVE: To provide a systematic analysis of TEs\' contribution in tissue-specific gene regulation, we examined the regulatory elements and genes in association with TE-derived regulatory sequences in 14 human cell lines belonging to 10 different tissue types using the functional genomics data from the ENCODE project. Specifically, we separately analyzed regulatory regions identified by three different approaches (DNase hypersensitive sites (DHS), histone active sites (HA), and histone repressive sites (HR)).
RESULTS: These regulatory regions showed to be distinct from each other by sharing less than 2.5% among all three types and more than 95% showed to be cell line-specific. Despite a lower total TE content overall than the genome average, each regulatory sequence type showed enrichment for one or two specific TE type(s): DHS for long terminal repeats (LTRs) and DNA transposons, HA for short interspersed nucleotide elements (SINEs), and HR for LTRs. In contrast, SINE was shown to be overrepresented in all three types of regulatory sequences located in gene-neighboring regions. TE-regulated genes were mostly shown to have cell line specific pattern, and tissue-specific genes (TSGs) showed higher usage of TE regulatory sequences in the tissue of their expression. While TEs in the regulatory sequences showed to be older than their genome-wide counterparts, younger TEs were shown to be more likely used in cell line specific regulatory sequences.
CONCLUSIONS: Collectively, our study provided further evidence enforcing an important contribution of TEs to tissue-specific gene regulation in humans.
目的:为了提供TEs在组织特异性基因调控中的贡献的系统分析,我们利用ENCODE项目的功能基因组学数据,在属于10种不同组织类型的14种人类细胞系中,检测了与TE衍生调控序列相关的调控元件和基因.具体来说,我们分别分析了通过三种不同方法识别的调控区(DNase超敏位点(DHS),组蛋白活性位点(HA),和组蛋白抑制位点(HR))。
结果:这些调控区显示出彼此不同,在所有三种类型中共享不到2.5%,超过95%显示出细胞系特异性。尽管总TE含量低于基因组平均值,每个调节序列类型显示富集一个或两个特定的TE类型(S):DHS长末端重复(LTR)和DNA转座子,用于短散布核苷酸元件(SINE)的HA,和HR为LTR。相比之下,在位于基因相邻区域的所有三种类型的调节序列中,SINE均表现出过多。TE调节的基因大多显示具有细胞系特异性模式,和组织特异性基因(TSGs)在其表达的组织中显示出较高的TE调控序列使用率。虽然调节序列中的TEs显示比它们的全基因组对应物更老,年轻的TE被证明更有可能用于细胞系特异性调节序列。
结论:总的来说,我们的研究提供了进一步的证据,证明了TEs对人类组织特异性基因调控的重要贡献.