Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS

Marta Barradas, Emma Anderton, Juan Carlos Acosta, SiDe Li, Ana Banito, Marc Rodriguez-Niedenführ, Goedele Maertens, Michaela Banck, Ming Ming Zhou, Martin J. Walsh, Gordon Peters, Jesús Gil

Research output: Contribution to journalArticle

234 Citations (Scopus)

Abstract

The INK4a/ARF tumor suppressor locus, a key executor of cellular senescence, is regulated by members of the Polycomb group (PcG) of transcriptional repressors. Here we show that signaling from oncogenic RAS overrides PcG-mediated repression of INK4a by activating the H3K27 demethylase JMJD3 and down-regulating the methyltransferase EZH2. In human fibroblasts, JMJD3 activates INK4a, but not ARF, and causes p16INK4a-dependent arrest. In mouse embryo fibroblasts, Jmjd3 activates both Ink4a and Arf and elicits a p53-dependent arrest, echoing the effects of RAS in this system. Our findings directly implicate JMJD3 in the regulation of INK4a/ARF during oncogene-induced senescence and suggest that JMJD3 has the capacity to act as a tumor suppressor.

Original languageEnglish (US)
Pages (from-to)1177-1182
Number of pages6
JournalGenes and Development
Volume23
Issue number10
DOIs
StatePublished - May 15 2009
Externally publishedYes

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Histone Demethylases
Epigenomics
Fibroblasts
Cell Aging
Methyltransferases
Oncogenes
Neoplasms
Embryonic Structures

Keywords

  • Histone methylation
  • INK4a
  • JmjC proteins
  • Polycomb
  • Senescence

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Medicine(all)

Cite this

Barradas, M., Anderton, E., Acosta, J. C., Li, S., Banito, A., Rodriguez-Niedenführ, M., ... Gil, J. (2009). Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS. Genes and Development, 23(10), 1177-1182. https://doi.org/10.1101/gad.511109

Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS. / Barradas, Marta; Anderton, Emma; Acosta, Juan Carlos; Li, SiDe; Banito, Ana; Rodriguez-Niedenführ, Marc; Maertens, Goedele; Banck, Michaela; Zhou, Ming Ming; Walsh, Martin J.; Peters, Gordon; Gil, Jesús.

In: Genes and Development, Vol. 23, No. 10, 15.05.2009, p. 1177-1182.

Research output: Contribution to journalArticle

Barradas, M, Anderton, E, Acosta, JC, Li, S, Banito, A, Rodriguez-Niedenführ, M, Maertens, G, Banck, M, Zhou, MM, Walsh, MJ, Peters, G & Gil, J 2009, 'Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS', Genes and Development, vol. 23, no. 10, pp. 1177-1182. https://doi.org/10.1101/gad.511109
Barradas M, Anderton E, Acosta JC, Li S, Banito A, Rodriguez-Niedenführ M et al. Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS. Genes and Development. 2009 May 15;23(10):1177-1182. https://doi.org/10.1101/gad.511109
Barradas, Marta ; Anderton, Emma ; Acosta, Juan Carlos ; Li, SiDe ; Banito, Ana ; Rodriguez-Niedenführ, Marc ; Maertens, Goedele ; Banck, Michaela ; Zhou, Ming Ming ; Walsh, Martin J. ; Peters, Gordon ; Gil, Jesús. / Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS. In: Genes and Development. 2009 ; Vol. 23, No. 10. pp. 1177-1182.
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