Nuclear pore density controls heterochromatin reorganization during senescence.
Cell Line
Cell Nucleus
/ metabolism
Cellular Senescence
/ physiology
Gene Knockdown Techniques
Heterochromatin
/ genetics
Humans
Models, Molecular
Nuclear Pore
/ genetics
Nuclear Pore Complex Proteins
/ genetics
Proto-Oncogene Proteins
/ genetics
RNA, Small Interfering
/ metabolism
Transcriptional Activation
/ genetics
inflammation
nuclear organization
nuclear pore
senescence
Journal
Genes & development
ISSN: 1549-5477
Titre abrégé: Genes Dev
Pays: United States
ID NLM: 8711660
Informations de publication
Date de publication:
01 02 2019
01 02 2019
Historique:
received:
26
09
2018
accepted:
04
12
2018
pubmed:
30
1
2019
medline:
26
2
2019
entrez:
30
1
2019
Statut:
ppublish
Résumé
During oncogene-induced senescence (OIS), heterochromatin is lost from the nuclear periphery and forms internal senescence-associated heterochromatin foci (SAHFs). We show that an increased nuclear pore density during OIS is responsible for SAHF formation. In particular, the nucleoporin TPR is necessary for both formation and maintenance of SAHFs. Loss of SAHFs does not affect cell cycle arrest but abrogates the senescence-associated secretory phenotype-a program of inflammatory cytokine gene activation. Our results uncover a previously unknown role of nuclear pores in heterochromatin reorganization in mammalian nuclei and demonstrate the importance of heterochromatin organization for a specific gene activation program.
Identifiants
pubmed: 30692205
pii: gad.321117.118
doi: 10.1101/gad.321117.118
pmc: PMC6362808
doi:
Substances chimiques
Heterochromatin
0
Nuclear Pore Complex Proteins
0
Proto-Oncogene Proteins
0
RNA, Small Interfering
0
TPR protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
144-149Subventions
Organisme : Medical Research Council
ID : MC_PC_U127527202
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K01563X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/2
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 Boumendil et al.; Published by Cold Spring Harbor Laboratory Press.
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