Nuclear pore density controls heterochromatin reorganization during senescence

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 neces...

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Bibliographic Details
Published in:Genes & development 2019-02, Vol.33 (3-4), p.144-149
Main Authors: Boumendil, Charlene, Hari, Priya, Olsen, Karl C F, Acosta, Juan Carlos, Bickmore, Wendy A
Format: Article
Language:English
Subjects:
Cell Line
Cell Nucleus - metabolism
Cellular Senescence - physiology
Gene Knockdown Techniques
Heterochromatin - genetics
Heterochromatin - metabolism
Humans
Models, Molecular
Nuclear Pore - genetics
Nuclear Pore - metabolism
Nuclear Pore Complex Proteins - genetics
Nuclear Pore Complex Proteins - metabolism
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Research Communication
RNA, Small Interfering - metabolism
Transcriptional Activation - genetics
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Summary: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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.321117.118