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LINE-1 Evasion of Epigenetic Repression in Humans.
Sanchez-Luque, Francisco J; Kempen, Marie-Jeanne H C; Gerdes, Patricia; Vargas-Landin, Dulce B; Richardson, Sandra R; Troskie, Robin-Lee; Jesuadian, J Samuel; Cheetham, Seth W; Carreira, Patricia E; Salvador-Palomeque, Carmen; García-Cañadas, Marta; Muñoz-Lopez, Martin; Sanchez, Laura; Lundberg, Mischa; Macia, Angela; Heras, Sara R; Brennan, Paul M; Lister, Ryan; Garcia-Perez, Jose L; Ewing, Adam D; Faulkner, Geoffrey J.
Affiliation
  • Sanchez-Luque FJ; Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia; GENYO Centre for Genomics and Oncological Research, Pfizer University of Granada, Andalusian Regional Government, Avda Ilustración, 114, PTS Granada 18016, Spain. Electronic address: francisco.sanch
  • Kempen MHC; Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
  • Gerdes P; Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.
  • Vargas-Landin DB; Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, the University of Western Australia, Perth, WA 6009, Australia; Harry Perkins Institute of Medical Research, Perth, WA 6009, Australia.
  • Richardson SR; Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.
  • Troskie RL; Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.
  • Jesuadian JS; Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.
  • Cheetham SW; Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.
  • Carreira PE; Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.
  • Salvador-Palomeque C; Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.
  • García-Cañadas M; GENYO Centre for Genomics and Oncological Research, Pfizer University of Granada, Andalusian Regional Government, Avda Ilustración, 114, PTS Granada 18016, Spain.
  • Muñoz-Lopez M; GENYO Centre for Genomics and Oncological Research, Pfizer University of Granada, Andalusian Regional Government, Avda Ilustración, 114, PTS Granada 18016, Spain.
  • Sanchez L; GENYO Centre for Genomics and Oncological Research, Pfizer University of Granada, Andalusian Regional Government, Avda Ilustración, 114, PTS Granada 18016, Spain.
  • Lundberg M; Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.
  • Macia A; Department of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Heras SR; GENYO Centre for Genomics and Oncological Research, Pfizer University of Granada, Andalusian Regional Government, Avda Ilustración, 114, PTS Granada 18016, Spain; Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, 18071 G
  • Brennan PM; Edinburgh Cancer Research Centre, Western General Hospital, Edinburgh, EH4 2XR, UK.
  • Lister R; Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, the University of Western Australia, Perth, WA 6009, Australia; Harry Perkins Institute of Medical Research, Perth, WA 6009, Australia.
  • Garcia-Perez JL; GENYO Centre for Genomics and Oncological Research, Pfizer University of Granada, Andalusian Regional Government, Avda Ilustración, 114, PTS Granada 18016, Spain; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Western General Hospital, Edinburg
  • Ewing AD; Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.
  • Faulkner GJ; Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia; Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: faulknergj@gmail.com.
Mol Cell ; 75(3): 590-604.e12, 2019 08 08.
Article in En | MEDLINE | ID: mdl-31230816
Epigenetic silencing defends against LINE-1 (L1) retrotransposition in mammalian cells. However, the mechanisms that repress young L1 families and how L1 escapes to cause somatic genome mosaicism in the brain remain unclear. Here we report that a conserved Yin Yang 1 (YY1) transcription factor binding site mediates L1 promoter DNA methylation in pluripotent and differentiated cells. By analyzing 24 hippocampal neurons with three distinct single-cell genomic approaches, we characterized and validated a somatic L1 insertion bearing a 3' transduction. The source (donor) L1 for this insertion was slightly 5' truncated, lacked the YY1 binding site, and was highly mobile when tested in vitro. Locus-specific bisulfite sequencing revealed that the donor L1 and other young L1s with mutated YY1 binding sites were hypomethylated in embryonic stem cells, during neurodifferentiation, and in liver and brain tissue. These results explain how L1 can evade repression and retrotranspose in the human body.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Retroelements / Long Interspersed Nucleotide Elements / YY1 Transcription Factor / Epigenetic Repression Limits: Humans Language: En Journal: Mol Cell Journal subject: BIOLOGIA MOLECULAR Year: 2019 Type: Article
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Retroelements / Long Interspersed Nucleotide Elements / YY1 Transcription Factor / Epigenetic Repression Limits: Humans Language: En Journal: Mol Cell Journal subject: BIOLOGIA MOLECULAR Year: 2019 Type: Article