Evolution of Alu elements toward enhancers.
The 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.
Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China; Center of Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Lincui East Road, Beijing 100101, China.
Ming
M
Su
Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China; Center of Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Lincui East Road, Beijing 100101, China.
Dali
D
Han
Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Jerome
J
Boyd-Kirkup
Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China; Center of Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Lincui East Road, Beijing 100101, China.
Xiaoming
X
Yu
Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China. Electronic address: jdhan@picb.ac.cn.
Jing-Dong J
JJ
Han
D020087:Alu Elements / Q000235:genetics*; D000818:Animals; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D019143:Evolution, Molecular; D015894:Genome, Human; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic
D006657:Histones