Latent Regulatory Potential of Human-Specific Repetitive Elements

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,...

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Bibliographic Details
Published in:Molecular cell 2013-01, Vol.49 (2), p.262-272
Main Authors: Ward, Michelle C., Wilson, Michael D., Barbosa-Morais, Nuno L., Schmidt, Dominic, Stark, Rory, Pan, Qun, Schwalie, Petra C., Menon, Suraj, Lukk, Margus, Watt, Stephen, Thybert, David, Kutter, Claudia, Kirschner, Kristina, Flicek, Paul, Blencowe, Benjamin J., Odom, Duncan T.
Format: Article
Language:English
Subjects:
Animals
chromosomes
Chromosomes, Human, Pair 21 - genetics
Chromosomes, Human, Pair 21 - metabolism
DNA Methylation
DNA Transposable Elements
epigenetics
Female
females
gene expression
Gene Silencing
genome
germ cells
histones
Histones - metabolism
Humans
Kidney - metabolism
Liver - metabolism
Male
Mice
Mice, Inbred C57BL
Organ Specificity
Protein Binding
Species Specificity
Testis - metabolism
transcription (genetics)
Transcription Factors - metabolism
Transcription Initiation, Genetic
Transcriptional Activation
transposons
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Summary: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. ► A mouse carrying human chromosome 21 fails to repress primate-specific repeats ► The lack of repression was revealed by H3K4me3 and transcription factor binding ► Activation corresponded to a decrease in CpG methylation ► Primate-specific repeats activated in human testes were activated in the Tc1 mouse
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2012.11.013