Ndy1/KDM2B immortalizes mouse embryonic fibroblasts by repressing the Ink4a/Arf locus

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Ndy1/KDM2B immortalizes mouse embryonic fibroblasts by repressing the Ink4a/Arf locus. / Tzatsos, Alexandros; Pfau, Raymond; Kampranis, Sotirios; Tsichlis, Philip N.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 8, 24.02.2009, p. 2641-6.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Tzatsos, A, Pfau, R, Kampranis, S & Tsichlis, PN 2009, 'Ndy1/KDM2B immortalizes mouse embryonic fibroblasts by repressing the Ink4a/Arf locus', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 8, pp. 2641-6. https://doi.org/10.1073/pnas.0813139106

APA

Tzatsos, A., Pfau, R., Kampranis, S., & Tsichlis, P. N. (2009). Ndy1/KDM2B immortalizes mouse embryonic fibroblasts by repressing the Ink4a/Arf locus. Proceedings of the National Academy of Sciences of the United States of America, 106(8), 2641-6. https://doi.org/10.1073/pnas.0813139106

Vancouver

Tzatsos A, Pfau R, Kampranis S, Tsichlis PN. Ndy1/KDM2B immortalizes mouse embryonic fibroblasts by repressing the Ink4a/Arf locus. Proceedings of the National Academy of Sciences of the United States of America. 2009 Feb 24;106(8):2641-6. https://doi.org/10.1073/pnas.0813139106

Author

Tzatsos, Alexandros ; Pfau, Raymond ; Kampranis, Sotirios ; Tsichlis, Philip N. / Ndy1/KDM2B immortalizes mouse embryonic fibroblasts by repressing the Ink4a/Arf locus. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 8. pp. 2641-6.

Bibtex

@article{9eee4d8b4aa54f6d951f666c5636ff89,
title = "Ndy1/KDM2B immortalizes mouse embryonic fibroblasts by repressing the Ink4a/Arf locus",
abstract = "The histone H3 demethylase Not dead yet-1 (Ndy1/KDM2B) is a physiological inhibitor of senescence. Here, we show that Ndy1 is down-regulated during senescence in mouse embryonic fibroblasts (MEFs) and that it represses the Ink4a/Arf locus. Ndy1 counteracts the senescence-associated down-regulation of Ezh2, a component of polycomb-repressive complex (PRC) 2, via a JmjC domain-dependent process leading to the global and Ink4a/Arf locus-specific up-regulation of histone H3K27 trimethylation. The latter promotes the Ink4a/Arf locus-specific binding of Bmi1, a component of PRC1. Ndy1, which interacts with Ezh2, also binds the Ink4a/Arf locus and demethylates the locus-associated histone H3K36me2 and histone H3K4me3. The combination of histone modifications driven by Ndy1 interferes with the binding of RNA Polymerase II, resulting in the transcriptional silencing of the Ink4a/Arf locus and contributing to the Ndy1 immortalization phenotype. Other studies show that, in addition to inhibiting replicative senescence, Ndy1 inhibits Ras oncogene-induced senescence via a similar molecular mechanism.",
keywords = "Animals, Cell Aging, Cell Line, Transformed, Cyclin-Dependent Kinase Inhibitor p16, Fibroblasts, Gene Expression Regulation, Developmental, Histone-Lysine N-Methyltransferase, Histones, Methylation, Mice, Nuclear Proteins, Oxidoreductases, N-Demethylating, Polycomb Repressive Complex 1, Polycomb Repressive Complex 2, Proto-Oncogene Proteins, Repressor Proteins, Up-Regulation",
author = "Alexandros Tzatsos and Raymond Pfau and Sotirios Kampranis and Tsichlis, {Philip N}",
year = "2009",
month = feb,
day = "24",
doi = "10.1073/pnas.0813139106",
language = "English",
volume = "106",
pages = "2641--6",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "8",

}

RIS

TY - JOUR

T1 - Ndy1/KDM2B immortalizes mouse embryonic fibroblasts by repressing the Ink4a/Arf locus

AU - Tzatsos, Alexandros

AU - Pfau, Raymond

AU - Kampranis, Sotirios

AU - Tsichlis, Philip N

PY - 2009/2/24

Y1 - 2009/2/24

N2 - The histone H3 demethylase Not dead yet-1 (Ndy1/KDM2B) is a physiological inhibitor of senescence. Here, we show that Ndy1 is down-regulated during senescence in mouse embryonic fibroblasts (MEFs) and that it represses the Ink4a/Arf locus. Ndy1 counteracts the senescence-associated down-regulation of Ezh2, a component of polycomb-repressive complex (PRC) 2, via a JmjC domain-dependent process leading to the global and Ink4a/Arf locus-specific up-regulation of histone H3K27 trimethylation. The latter promotes the Ink4a/Arf locus-specific binding of Bmi1, a component of PRC1. Ndy1, which interacts with Ezh2, also binds the Ink4a/Arf locus and demethylates the locus-associated histone H3K36me2 and histone H3K4me3. The combination of histone modifications driven by Ndy1 interferes with the binding of RNA Polymerase II, resulting in the transcriptional silencing of the Ink4a/Arf locus and contributing to the Ndy1 immortalization phenotype. Other studies show that, in addition to inhibiting replicative senescence, Ndy1 inhibits Ras oncogene-induced senescence via a similar molecular mechanism.

AB - The histone H3 demethylase Not dead yet-1 (Ndy1/KDM2B) is a physiological inhibitor of senescence. Here, we show that Ndy1 is down-regulated during senescence in mouse embryonic fibroblasts (MEFs) and that it represses the Ink4a/Arf locus. Ndy1 counteracts the senescence-associated down-regulation of Ezh2, a component of polycomb-repressive complex (PRC) 2, via a JmjC domain-dependent process leading to the global and Ink4a/Arf locus-specific up-regulation of histone H3K27 trimethylation. The latter promotes the Ink4a/Arf locus-specific binding of Bmi1, a component of PRC1. Ndy1, which interacts with Ezh2, also binds the Ink4a/Arf locus and demethylates the locus-associated histone H3K36me2 and histone H3K4me3. The combination of histone modifications driven by Ndy1 interferes with the binding of RNA Polymerase II, resulting in the transcriptional silencing of the Ink4a/Arf locus and contributing to the Ndy1 immortalization phenotype. Other studies show that, in addition to inhibiting replicative senescence, Ndy1 inhibits Ras oncogene-induced senescence via a similar molecular mechanism.

KW - Animals

KW - Cell Aging

KW - Cell Line, Transformed

KW - Cyclin-Dependent Kinase Inhibitor p16

KW - Fibroblasts

KW - Gene Expression Regulation, Developmental

KW - Histone-Lysine N-Methyltransferase

KW - Histones

KW - Methylation

KW - Mice

KW - Nuclear Proteins

KW - Oxidoreductases, N-Demethylating

KW - Polycomb Repressive Complex 1

KW - Polycomb Repressive Complex 2

KW - Proto-Oncogene Proteins

KW - Repressor Proteins

KW - Up-Regulation

U2 - 10.1073/pnas.0813139106

DO - 10.1073/pnas.0813139106

M3 - Journal article

C2 - 19202064

VL - 106

SP - 2641

EP - 2646

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 8

ER -

ID: 159085042