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

doi:10.1101/gad.511109

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 journal › Article › peer-review

Abstract / Description of output

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 p16(INK4a)-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 language	English
Pages (from-to)	1177-1182
Number of pages	6
Journal	Genes & Development
Volume	23
Issue number	10
DOIs	https://doi.org/10.1101/gad.511109
Publication status	Published - 15 May 2009

Keywords / Materials (for Non-textual outputs)

Cyclin-Dependent Kinase Inhibitor p16
Animals
ras Proteins
Jumonji Domain-Containing Histone Demethylases
Cell Aging
Humans
Oxidoreductases, N-Demethylating
Mice
Gene Expression Regulation
Epigenesis, Genetic
Signal Transduction
Fibroblasts

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10.1101/gad.511109

http://genesdev.cshlp.org/content/23/10/1177

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title = "Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS",

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 p16(INK4a)-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.",

keywords = "Cyclin-Dependent Kinase Inhibitor p16, Animals, ras Proteins, Jumonji Domain-Containing Histone Demethylases, Cell Aging, Humans, Oxidoreductases, N-Demethylating, Mice, Gene Expression Regulation, Epigenesis, Genetic, Signal Transduction, Fibroblasts",

author = "Marta Barradas and Emma Anderton and Acosta, {Juan Carlos} and Side Li and Ana Banito and Marc Rodriguez-Niedenf{\"u}hr and Goedele Maertens and Michaela Banck and Ming-Ming Zhou and Walsh, {Martin J} and Gordon Peters and Jes{\'u}s Gil",

year = "2009",

month = may,

day = "15",

doi = "10.1101/gad.511109",

language = "English",

volume = "23",

pages = "1177--1182",

journal = "Genes & Development",

issn = "1549-5477",

publisher = "Cold Spring Harbor Laboratory Press",

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TY - JOUR

T1 - Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS

AU - Barradas, Marta

AU - Anderton, Emma

AU - Acosta, Juan Carlos

AU - Li, Side

AU - Banito, Ana

AU - Rodriguez-Niedenführ, Marc

AU - Maertens, Goedele

AU - Banck, Michaela

AU - Zhou, Ming-Ming

AU - Walsh, Martin J

AU - Peters, Gordon

AU - Gil, Jesús

PY - 2009/5/15

Y1 - 2009/5/15

N2 - 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 p16(INK4a)-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.

AB - 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 p16(INK4a)-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.

KW - Cyclin-Dependent Kinase Inhibitor p16

KW - Animals

KW - ras Proteins

KW - Jumonji Domain-Containing Histone Demethylases

KW - Cell Aging

KW - Humans

KW - Oxidoreductases, N-Demethylating

KW - Mice

KW - Gene Expression Regulation

KW - Epigenesis, Genetic

KW - Signal Transduction

KW - Fibroblasts

U2 - 10.1101/gad.511109

DO - 10.1101/gad.511109

M3 - Article

C2 - 19451218

SN - 1549-5477

VL - 23

SP - 1177

EP - 1182

JO - Genes & Development

JF - Genes & Development

IS - 10

ER -

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

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Keywords / Materials (for Non-textual outputs)

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