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  • 1
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    L1 retrotransposition in human neural progenitor cells (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-08-07
    Description: Long interspersed element 1 (LINE-1 or L1) retrotransposons have markedly affected the human genome. L1s must retrotranspose in the germ line or during early development to ensure their evolutionary success, yet the extent to which this process affects somatic cells is poorly understood. We previously demonstrated that engineered human L1s can retrotranspose in adult rat hippocampus progenitor cells in vitro and in the mouse brain in vivo. Here we demonstrate that neural progenitor cells isolated from human fetal brain and derived from human embryonic stem cells support the retrotransposition of engineered human L1s in vitro. Furthermore, we developed a quantitative multiplex polymerase chain reaction that detected an increase in the copy number of endogenous L1s in the hippocampus, and in several regions of adult human brains, when compared to the copy number of endogenous L1s in heart or liver genomic DNAs from the same donor. These data suggest that de novo L1 retrotransposition events may occur in the human brain and, in principle, have the potential to contribute to individual somatic mosaicism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909034/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909034/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coufal, Nicole G -- Garcia-Perez, Jose L -- Peng, Grace E -- Yeo, Gene W -- Mu, Yangling -- Lovci, Michael T -- Morell, Maria -- O'Shea, K Sue -- Moran, John V -- Gage, Fred H -- GM069985/GM/NIGMS NIH HHS/ -- GM082970/GM/NIGMS NIH HHS/ -- MH082070/MH/NIMH NIH HHS/ -- NS048187/NS/NINDS NIH HHS/ -- P20 GM069985/GM/NIGMS NIH HHS/ -- P20 GM069985-010001/GM/NIGMS NIH HHS/ -- R01 GM060518/GM/NIGMS NIH HHS/ -- R01 GM082970/GM/NIGMS NIH HHS/ -- R01 GM082970-03/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Aug 27;460(7259):1127-31. doi: 10.1038/nature08248. Epub 2009 Aug 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19657334" target="_blank"〉PubMed〈/a〉
    Keywords: 5' Untranslated Regions/genetics ; Brain/cytology ; Cell Line ; Chromatin Immunoprecipitation ; DNA Methylation ; Embryonic Stem Cells/*cytology/*metabolism ; Fetus/cytology ; Gene Dosage ; Humans ; Neurons/*cytology/*metabolism ; Polymerase Chain Reaction ; Retroelements/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1) retrotransposition in human neural stem cells (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-12-09
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 3
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    Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1) retrotransposition in human neural stem cells [Neuroscience] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-12-21
    Description: Long interspersed element-1 (L1) retrotransposons compose ∼20% of the mammalian genome, and ongoing L1 retrotransposition events can impact genetic diversity by various mechanisms. Previous studies have demonstrated that endogenous L1 retrotransposition can occur in the germ line and during early embryonic development. In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients. Here, we demonstrate an increase in the retrotransposition efficiency of engineered human L1s in cells that lack or contain severely reduced levels of ataxia telangiectasia mutated, a serine/threonine kinase involved in DNA damage signaling and neurodegenerative disease. We demonstrate that the increase in L1 retrotransposition in ataxia telangiectasia mutated-deficient cells most likely occurs by conventional target-site primed reverse transcription and generate either longer, or perhaps more, L1 retrotransposition events per cell. Finally, we provide evidence suggesting an increase in human-specific L1 DNA copy number in postmortem brain tissue derived from ataxia telangiectasia patients compared with healthy controls. Together, these data suggest that cellular proteins involved in the DNA damage response may modulate L1 retrotransposition.
    Keywords: Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes Sackler Special Feature
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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