Imaging the response to DNA damage in heterochromatin domains reveals core principles of heterochromatin maintenance.
Animals
Cell Line, Tumor
Chromatin Assembly and Disassembly
/ genetics
DNA
/ genetics
DNA Damage
DNA Repair
DNA-Binding Proteins
/ genetics
Heterochromatin
/ genetics
Histone-Lysine N-Methyltransferase
/ genetics
Histones
/ metabolism
Humans
MCF-7 Cells
Methylation
Mice
NIH 3T3 Cells
Ultraviolet Rays
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 04 2021
23 04 2021
Historique:
received:
27
07
2020
accepted:
17
03
2021
entrez:
24
4
2021
pubmed:
25
4
2021
medline:
11
5
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33893291
doi: 10.1038/s41467-021-22575-5
pii: 10.1038/s41467-021-22575-5
pmc: PMC8065061
doi:
Substances chimiques
DDB2 protein, human
0
DNA-Binding Proteins
0
Heterochromatin
0
Histones
0
DNA
9007-49-2
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
SETDB1 protein, human
EC 2.1.1.43
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2428Références
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