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Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine.
Hackett, Jamie A; Sengupta, Roopsha; Zylicz, Jan J; Murakami, Kazuhiro; Lee, Caroline; Down, Thomas A; Surani, M Azim.
Afiliación
  • Hackett JA; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, United Kingdom.
  • Sengupta R; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, United Kingdom.
  • Zylicz JJ; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, United Kingdom.
  • Murakami K; Wellcome Trust/MRC Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Lee C; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, United Kingdom.
  • Down TA; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, United Kingdom.
  • Surani MA; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, United Kingdom.
Science ; 339(6118): 448-52, 2013 Jan 25.
Article en En | MEDLINE | ID: mdl-23223451
ABSTRACT
Mouse primordial germ cells (PGCs) undergo sequential epigenetic changes and genome-wide DNA demethylation to reset the epigenome for totipotency. Here, we demonstrate that erasure of CpG methylation (5mC) in PGCs occurs via conversion to 5-hydroxymethylcytosine (5hmC), driven by high levels of TET1 and TET2. Global conversion to 5hmC initiates asynchronously among PGCs at embryonic day (E) 9.5 to E10.5 and accounts for the unique process of imprint erasure. Mechanistically, 5hmC enrichment is followed by its protracted decline thereafter at a rate consistent with replication-coupled dilution. The conversion to 5hmC is an important component of parallel redundant systems that drive comprehensive reprogramming in PGCs. Nonetheless, we identify rare regulatory elements that escape systematic DNA demethylation in PGCs, providing a potential mechanistic basis for transgenerational epigenetic inheritance.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Impresión Genómica / Metilación de ADN / Citosina / Epigénesis Genética / Embrión de Mamíferos / Células Germinativas Límite: Animals Idioma: En Revista: Science Año: 2013 Tipo del documento: Article País de afiliación: Reino Unido

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Impresión Genómica / Metilación de ADN / Citosina / Epigénesis Genética / Embrión de Mamíferos / Células Germinativas Límite: Animals Idioma: En Revista: Science Año: 2013 Tipo del documento: Article País de afiliación: Reino Unido