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Imaging the response to DNA damage in heterochromatin domains reveals core principles of heterochromatin maintenance.
Fortuny, Anna; Chansard, Audrey; Caron, Pierre; Chevallier, Odile; Leroy, Olivier; Renaud, Olivier; Polo, Sophie E.
Afiliação
  • Fortuny A; Epigenetics and Cell Fate Centre, UMR7216 CNRS, Université de Paris, Paris, France.
  • Chansard A; Epigenetics and Cell Fate Centre, UMR7216 CNRS, Université de Paris, Paris, France.
  • Caron P; Epigenetics and Cell Fate Centre, UMR7216 CNRS, Université de Paris, Paris, France.
  • Chevallier O; Epigenetics and Cell Fate Centre, UMR7216 CNRS, Université de Paris, Paris, France.
  • Leroy O; Cell and Tissue Imaging Facility, UMR3215 PICT-IBiSA, Institut Curie, Paris, France.
  • Renaud O; Cell and Tissue Imaging Facility, UMR3215 PICT-IBiSA, Institut Curie, Paris, France.
  • Polo SE; Epigenetics and Cell Fate Centre, UMR7216 CNRS, Université de Paris, Paris, France. sophie.polo@univ-paris-diderot.fr.
Nat Commun ; 12(1): 2428, 2021 04 23.
Article em En | MEDLINE | ID: mdl-33893291
ABSTRACT
Heterochromatin is a critical chromatin compartment, whose integrity governs genome stability and cell fate transitions. How heterochromatin features, including higher-order chromatin folding and histone modifications associated with transcriptional silencing, are maintained following a genotoxic stress challenge is unknown. Here, we establish a system for targeting UV damage to pericentric heterochromatin in mammalian cells and for tracking the heterochromatin response to UV in real time. We uncover profound heterochromatin compaction changes during repair, orchestrated by the UV damage sensor DDB2, which stimulates linker histone displacement from chromatin. Despite massive heterochromatin unfolding, heterochromatin-specific histone modifications and transcriptional silencing are maintained. We unveil a central role for the methyltransferase SETDB1 in the maintenance of heterochromatic histone marks after UV. SETDB1 coordinates histone methylation with new histone deposition in damaged heterochromatin, thus protecting cells from genome instability. Our data shed light on fundamental molecular mechanisms safeguarding higher-order chromatin integrity following DNA damage.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / DNA / Heterocromatina / Reparo do DNA Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / DNA / Heterocromatina / Reparo do DNA Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article