کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2040550 | 1073117 | 2014 | 10 صفحه PDF | دانلود رایگان |
• Alus are bound by two well-phased nucleosomes with enhancer-like active modifications
• Similar to enhancers, enrichment of H3K4 monomethylation on Alu is tissue specific
• Alus preferentially interact with promoters and are enriched for regulatory motifs
• Genomic/epigenomic features of Alus follow proto-enhancer evolutionary continuum
SummaryThe human genome contains approximately one million Alu repetitive elements comprising 10% of the genome, yet their functions are not well understood. Here, we show that Alu elements resemble enhancers. Alu elements are bound by two well-phased nucleosomes that contain histones bearing marks of active chromatin, and they show tissue-specific enrichment for the enhancer mark H3K4me1. A proportion of Alu elements were experimentally validated as bona fide active enhancers with an in vitro reporter assay. In addition, Hi-C data indicate that Alus show long-range interactions with gene promoters. We also find that Alus are generally more conserved when located in the proximal upstream region of genes. Their similarity to enhancers becomes more prominent with their age in the human genome, following a clear evolutionary continuum reminiscent of the evolutionary pattern of proto-genes. Therefore, we conclude that some Alu elements can function as enhancers and propose that many more may be proto-enhancers that serve as a repertoire for the de novo birth of enhancers.
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Journal: - Volume 7, Issue 2, 24 April 2014, Pages 376–385