School of Biology, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
PLoS One. 2011;6(11):e27513. doi: 10.1371/journal.pone.0027513. Epub 2011 Nov 7.
Experimentally characterized enhancer regions have previously been shown to display specific patterns of enrichment for several different histone modifications. We modelled these enhancer chromatin profiles in the human genome and used them to guide the search for novel enhancers derived from transposable element (TE) sequences. To do this, a computational approach was taken to analyze the genome-wide histone modification landscape characterized by the ENCODE project in two human hematopoietic cell types, GM12878 and K562. We predicted the locations of 2,107 and 1,448 TE-derived enhancers in the GM12878 and K562 cell lines respectively. A vast majority of these putative enhancers are unique to each cell line; only 3.5% of the TE-derived enhancers are shared between the two. We evaluated the functional effect of TE-derived enhancers by associating them with the cell-type specific expression of nearby genes, and found that the number of TE-derived enhancers is strongly positively correlated with the expression of nearby genes in each cell line. Furthermore, genes that are differentially expressed between the two cell lines also possess a divergent number of TE-derived enhancers in their vicinity. As such, genes that are up-regulated in the GM12878 cell line and down-regulated in K562 have significantly more TE-derived enhancers in their vicinity in the GM12878 cell line and vice versa. These data indicate that human TE-derived sequences are likely to be involved in regulating cell-type specific gene expression on a broad scale and suggest that the enhancer activity of TE-derived sequences is mediated by epigenetic regulatory mechanisms.
先前的研究已经表明，实验鉴定的增强子区域具有几种不同组蛋白修饰的特定富集模式。我们对人类基因组中的这些增强子染色质进行了建模，并利用这些模型来指导从转座元件 (TE) 序列中寻找新的增强子。为此，我们采用了一种计算方法，分析了两个人类造血细胞系（GM12878 和 K562）中 ENCODE 项目所描述的全基因组组蛋白修饰景观。我们分别预测了 GM12878 和 K562 细胞系中 2107 个和 1448 个 TE 衍生增强子的位置。这些假定的增强子绝大多数是每个细胞系特有的；只有 3.5%的 TE 衍生增强子在两种细胞系之间共享。我们通过将 TE 衍生增强子与附近基因的细胞类型特异性表达相关联，评估了它们的功能效应，发现 TE 衍生增强子的数量与每个细胞系中附近基因的表达呈强烈正相关。此外，在两种细胞系之间表达差异的基因在其附近也具有不同数量的 TE 衍生增强子。因此，在 GM12878 细胞系中上调而在 K562 细胞系中下调的基因在 GM12878 细胞系中其附近具有显著更多的 TE 衍生增强子，反之亦然。这些数据表明，人类 TE 衍生序列可能广泛参与调节细胞类型特异性基因表达，并表明 TE 衍生序列的增强子活性是由表观遗传调控机制介导的。
