4.8 Article

Imaging the response to DNA damage in heterochromatin domains reveals core principles of heterochromatin maintenance

Journal

NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-021-22575-5

Keywords

-

Funding

  1. European Research Council (ERC) [ERC-2013-StG-336427, ERC-2018-CoG-818625]
  2. French National Research Agency [ANR-12-JSV6-0002-01, ANR-18-CE12-0017-01]
  3. Who am I? laboratory of excellence - French Government through its Investments for the Future programme [ANR-11-LABX-0071, ANR-11-IDEX-0005-01]
  4. EDF Radiobiology programme [RB 2014-01]
  5. Fondation ARC [PDF20190509195]
  6. France BioImaging [ANR-10-INBS-04]
  7. University of Paris
  8. Fondation Recherche Medicale [ARF201909009206]
  9. Agence Nationale de la Recherche (ANR) [ANR-18-CE12-0017] Funding Source: Agence Nationale de la Recherche (ANR)

Ask authors/readers for more resources

Heterochromatin is a critical chromatin compartment that plays a key role in genome stability and cell fate transitions. This study reveals how heterochromatin features are preserved following a genotoxic stress challenge by tracking the heterochromatin response to UV damage in real time.
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. The heterochromatin compartment is key for genome stability and cell fate transitions. Here, by tracking the heterochromatin response to UV damage in real time, the authors reveal how heterochromatin features are preserved following a genotoxic stress challenge.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available