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Nuclear pore density controls heterochromatin reorganization during senescence.

ABSTRACT: 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.

SUBMITTER: Boumendil C

PROVIDER: S-EPMC6362808 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Nuclear pore density controls heterochromatin reorganization during senescence.

Boumendil Charlene C Hari Priya P Olsen Karl C F KCF Acosta Juan Carlos JC Bickmore Wendy A WA

Genes & development 20190128 3-4

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 ac ...[more]

PMID: 30692205

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