@article{f816cfd3c08f42b1b497f41b49d6452d,
title = "Latent Regulatory Potential of Human-Specific Repetitive Elements",
abstract = "At least half of the human genome is derived from repetitive elements, which are often lineage specific and silenced by a variety of genetic and epigenetic mechanisms. Using a transchromosomic mouse strain that transmits an almost complete single copy of human chromosome 21 via the female germline, we show that a heterologous regulatory environment can transcriptionally activate transposon-derived human regulatory regions. In the mouse nucleus, hundreds of locations on human chromosome 21 newly associate with activating histone modifications in both somatic and germline tissues, and influence the gene expression of nearby transcripts. These regions are enriched with primate and human lineage-specific transposable elements, and their activation corresponds to changes in DNA methylation at CpG dinucleotides. This study reveals the latent regulatory potential of the repetitive human genome and illustrates the species specificity of mechanisms that control it.",
author = "Ward, {Michelle C.} and Wilson, {Michael D.} and Barbosa-Morais, {Nuno L.} and Dominic Schmidt and Rory Stark and Qun Pan and Schwalie, {Petra C.} and Suraj Menon and Margus Lukk and Stephen Watt and David Thybert and Claudia Kutter and Kristina Kirschner and Paul Flicek and Blencowe, {Benjamin J.} and Odom, {Duncan T.}",
note = "Funding Information: We are grateful to J. Hadfield and the University of Cambridge Cancer Research UK Cambridge Institute Genomics Core, the Bioinformatics and Biological Resources Cores, and the Cambridge Genomics Service for running the human DNA methylation arrays. Thanks to G. Brown for computational assistance; V. Tybulewic and E. Fisher for providing Tc1 mice and mice tissues; and Dr. Hiroshi Kimura, Dr. Masashi Narita, and Dr. Robert J. White for providing antibodies. This research was supported by ERC Starting Grant and EMBO Young Investigator Award (D.T.O.), Wellcome Trust Awards WT062023 and WT098051 (D.T.O., P.F.), University of Cambridge (D.T.O., M.C.W., M.D.W., D.S., P.C.S.), Cancer Research UK (D.T.O., M.C.W., M.D.W., D.S., R.S., S.M., M.L., S.W., C.K., K.K.), EMBL (P.C.S., D.T., P.F.), Canadian Institutes for Health Research (N.L.B.-M., B.J.B.), Commonwealth Scholarship Commission (M.C.W.), European Commission Marie Curie Actions (N.L.B.-M.), and Swiss National Science Foundation (C.K.). M.C.W., M.D.W., and D.T.O. designed experiments; M.C.W., M.D.W., D.S., Q.P., C.K., S.W., and K.K. performed experiments; M.C.W., M.D.W., N.L.B.-M., D.S., P.C.S., R.S., Q.P., D.T., M.L., and S.M. analyzed data; M.C.W., M.D.W., and D.T.O. wrote the manuscript. M.D.W., B.J.B., P.F., and D.T.O. oversaw the work. ",
year = "2013",
month = jan,
day = "24",
doi = "10.1016/j.molcel.2012.11.013",
language = "English (US)",
volume = "49",
pages = "262--272",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "2",
}