LINE-1 Evasion of Epigenetic Repression in Humans.

Binding Sites / genetics DNA Methylation / genetics DNA-Binding Proteins / genetics Epigenetic Repression / genetics Genome, Human / genetics Hippocampus / metabolism Humans Liver / metabolism Long Interspersed Nucleotide Elements / genetics Neurons / metabolism Retroelements / genetics Single-Cell Analysis YY1 Transcription Factor / genetics
DNA methylation L1 LINE-1 YY1 epigenetics neuroscience retrotransposon single-cell genomics

Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
08 08 2019
Historique:
received: 11 10 2018
revised: 08 04 2019
accepted: 15 05 2019
pubmed: 25 6 2019
medline: 17 1 2020
entrez: 25 6 2019
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.molcel.2019.05.024 PMID: 31230816
pubmed: 31230816
pii: S1097-2765(19)30396-X
doi: 10.1016/j.molcel.2019.05.024
pii:
doi:

Substances chimiques

DNA-Binding Proteins 0
Retroelements 0
YY1 Transcription Factor 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

590-604.e12

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Auteurs

Francisco J 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.sanchezluque@mater.uq.edu.au.

Marie-Jeanne H C 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.

Patricia Gerdes (P)

Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.

Dulce B 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.

Sandra R Richardson (SR)

Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.

Robin-Lee Troskie (RL)

Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.

J Samuel Jesuadian (JS)

Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.

Seth W Cheetham (SW)

Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.

Patricia E Carreira (PE)

Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.

Carmen Salvador-Palomeque (C)

Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.

Marta García-Cañadas (M)

GENYO Centre for Genomics and Oncological Research, Pfizer University of Granada, Andalusian Regional Government, Avda Ilustración, 114, PTS Granada 18016, Spain.

Martin Muñoz-Lopez (M)

GENYO Centre for Genomics and Oncological Research, Pfizer University of Granada, Andalusian Regional Government, Avda Ilustración, 114, PTS Granada 18016, Spain.

Laura Sanchez (L)

GENYO Centre for Genomics and Oncological Research, Pfizer University of Granada, Andalusian Regional Government, Avda Ilustración, 114, PTS Granada 18016, Spain.

Mischa Lundberg (M)

Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.

Angela Macia (A)

Department of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA, USA.

Sara R 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 Granada, Spain.

Paul M Brennan (PM)

Edinburgh Cancer Research Centre, Western General Hospital, Edinburgh, EH4 2XR, UK.

Ryan 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.

Jose L 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, Edinburgh EH4 2XU, UK.

Adam D Ewing (AD)

Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.

Geoffrey J 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.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

Recherchemedicale.com › Phénomènes chimiques › Phénomènes biochimiques › Sites de fixation › LINE-1 Evasion of Epigenetic Repression in Humans.
Recherchemedicale.com › Phénomènes génétiques › Méthylation de l'ADN › LINE-1 Evasion of Epigenetic Repression in Humans.
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines de liaison à l'ADN › LINE-1 Evasion of Epigenetic Repression in Humans.
Recherchemedicale.com › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Répression épigénétique › LINE-1 Evasion of Epigenetic Repression in Humans.
Recherchemedicale.com › Phénomènes génétiques › Structures génétiques › Génome › Génome humain › LINE-1 Evasion of Epigenetic Repression in Humans.
Recherchemedicale.com › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Hippocampe › LINE-1 Evasion of Epigenetic Repression in Humans.
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › LINE-1 Evasion of Epigenetic Repression in Humans.
Recherchemedicale.com › Système digestif › Foie › LINE-1 Evasion of Epigenetic Repression in Humans.
Recherchemedicale.com › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Séquences répétées dispersées › Rétroéléments › Éléments LINE › LINE-1 Evasion of Epigenetic Repression in Humans.
Recherchemedicale.com › Cellules › Neurones › LINE-1 Evasion of Epigenetic Repression in Humans.
Recherchemedicale.com › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Séquences répétées dispersées › Rétroéléments › LINE-1 Evasion of Epigenetic Repression in Humans.
Recherchemedicale.com › Techniques d'investigation › Techniques cytologiques › Analyse sur cellule unique › LINE-1 Evasion of Epigenetic Repression in Humans.
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs érythroïdes spécifiques › Facteur de transcription YY1 › LINE-1 Evasion of Epigenetic Repression in Humans.