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Genes Dev. 2019 Feb 1;33(3-4):144-149. doi: 10.1101/gad.321117.118. Epub 2019 Jan 28.

Nuclear pore density controls heterochromatin reorganization during senescence.

Author information

1
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom.
2
Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom.

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.

KEYWORDS:

inflammation; nuclear organization; nuclear pore; senescence

PMID:
30692205
PMCID:
PMC6362808
DOI:
10.1101/gad.321117.118
[Indexed for MEDLINE]
Free PMC Article

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