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.
authors.affiliation: University of Cambridge, Cancer Research UK-Cambridge Institute, Cambridge CB2 0RE, UK.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Ward
authors.forename: Michael D
authors.initials: MD
authors.lastname: Wilson
authors.forename: Nuno L
authors.initials: NL
authors.lastname: Barbosa-Morais
authors.forename: Dominic
authors.initials: D
authors.lastname: Schmidt
authors.forename: Rory
authors.initials: R
authors.lastname: Stark
authors.forename: Qun
authors.initials: Q
authors.lastname: Pan
authors.forename: Petra C
authors.initials: PC
authors.lastname: Schwalie
authors.forename: Suraj
authors.initials: S
authors.lastname: Menon
authors.forename: Margus
authors.initials: M
authors.lastname: Lukk
authors.forename: Stephen
authors.initials: S
authors.lastname: Watt
authors.forename: David
authors.initials: D
authors.lastname: Thybert
authors.forename: Claudia
authors.initials: C
authors.lastname: Kutter
authors.forename: Kristina
authors.initials: K
authors.lastname: Kirschner
authors.forename: Paul
authors.initials: P
authors.lastname: Flicek
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Blencowe
authors.forename: Duncan T
authors.initials: DT
authors.lastname: Odom
mesh_terms: D000818:Animals; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004251:DNA Transposable Elements; D005260:Female; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D011485:Protein Binding; D013045:Species Specificity; D013737:Testis / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D061785:Transcription Initiation, Genetic; D015533:Transcriptional Activation
chemical_list: D004251:DNA Transposable Elements; D006657:Histones; D014157:Transcription Factors