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Science 296 (5570): 1132-1136

Copyright © 2002 by the American Association for the Advancement of Science

A Complex with Chromatin Modifiers That Occupies E2F- and Myc-Responsive Genes in G0 Cells

Hidesato Ogawa,* Kei-ichiro Ishiguro,* Stefan Gaubatz,dagger David M. Livingston, Yoshihiro Nakataniddagger

E2F-6 contributes to gene silencing in a manner independent of retinoblastoma protein family members. To better elucidate the molecular mechanism of repression by E2F-6, we have purified the factor from cultured cells. E2F-6 is found in a multimeric protein complex that contains Mga and Max, and thus the complex can bind not only to the E2F-binding site but also to Myc- and Brachyury-binding sites. Moreover, the complex contains chromatin modifiers such as a novel histone methyltransferase that modifies lysine 9 of histone H3, HP1gamma , and Polycomb group (PcG) proteins. The E2F-6 complex preferentially occupies target promoters in G0 cells rather than in G1 cells. These data suggest that these chromatin modifiers contribute to silencing of E2F- and Myc-responsive genes in quiescent cells.

Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
*   These authors contributed equally to this work.

dagger    Present address: Institute for Molecular Biology and Tumor Research, Philipps-University Marburg, D-35032 Marburg, Germany.

ddagger    To whom correspondence should be addressed. E-mail: yoshihiro_nakatani{at}dfci.harvard.edu

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Nuclear Speckle-Associated Protein Pnn/DRS Binds to the Transcriptional Corepressor CtBP and Relieves CtBP- Mediated Repression of the E-Cadherin Gene.
R. Alpatov, G. C. Munguba, P. Caton, J. H. Joo, Y. Shi, Y. Shi, M. E. Hunt, and S. P. Sugrue (2004)
Mol. Cell. Biol. 24, 10223-10235
   Abstract »    Full Text »    PDF »
Increased expression of Drosophila Su(var)3-7 triggers Su(var)3-9-dependent heterochromatin formation.
M. Delattre, A. Spierer, Y. Jaquet, and P. Spierer (2004)
J. Cell Sci. 117, 6239-6247
   Abstract »    Full Text »    PDF »
A role for E2F6 in distinguishing G1/S- and G2/M-specific transcription.
P. H. Giangrande, W. Zhu, S. Schlisio, X. Sun, S. Mori, S. Gaubatz, and J. R. Nevins (2004)
Genes & Dev. 18, 2941-2951
   Abstract »    Full Text »    PDF »
Identification of a Drosophila Myb-E2F2/RBF transcriptional repressor complex.
P. W. Lewis, E. L. Beall, T. C. Fleischer, D. Georlette, A. J. Link, and M. R. Botchan (2004)
Genes & Dev. 18, 2929-2940
   Abstract »    Full Text »    PDF »
Therapeutic opportunities for cell cycle re-entry and cardiac regeneration.
K. M. Regula, M. J. Rzeszutek, D. Baetz, C. Seneviratne, and L. A. Kirshenbaum (2004)
Cardiovasc Res 64, 395-401
   Abstract »    Full Text »    PDF »
TIF1{delta}, a Novel HP1-interacting Member of the Transcriptional Intermediary Factor 1 (TIF1) Family Expressed by Elongating Spermatids.
K. Khetchoumian, M. Teletin, M. Mark, T. Lerouge, M. Cervino, M. Oulad-Abdelghani, P. Chambon, and R. Losson (2004)
J. Biol. Chem. 279, 48329-48341
   Abstract »    Full Text »    PDF »
TIN2 Binds TRF1 and TRF2 Simultaneously and Stabilizes the TRF2 Complex on Telomeres.
J. Z.-S. Ye, J. R. Donigian, M. van Overbeek, D. Loayza, Y. Luo, A. N. Krutchinsky, B. T. Chait, and T. de Lange (2004)
J. Biol. Chem. 279, 47264-47271
   Abstract »    Full Text »    PDF »
p55, the Drosophila Ortholog of RbAp46/RbAp48, Is Required for the Repression of dE2F2/RBF-Regulated Genes.
B. Taylor-Harding, U. K. Binne, M. Korenjak, A. Brehm, and N. J. Dyson (2004)
Mol. Cell. Biol. 24, 9124-9136
   Abstract »    Full Text »    PDF »
E2F-1 Regulates the Expression of a Subset of Target Genes during Skeletal Myoblast Hypertrophy.
M. Hlaing, P. Spitz, K. Padmanabhan, B. Cabezas, C. S. Barker, and H. S. Bernstein (2004)
J. Biol. Chem. 279, 43625-43633
   Abstract »    Full Text »    PDF »
Epigenetics and cancer.
A. H. Lund and M. van Lohuizen (2004)
Genes & Dev. 18, 2315-2335
   Abstract »    Full Text »    PDF »
In silico identification of transcriptional regulators associated with c-Myc.
R. Elkon, K. I. Zeller, C. Linhart, C. V. Dang, R. Shamir, and Y. Shiloh (2004)
Nucleic Acids Res. 32, 4955-4961
   Abstract »    Full Text »    PDF »
Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals.
K. E. Luker, M. C. P. Smith, G. D. Luker, S. T. Gammon, H. Piwnica-Worms, and D. Piwnica-Worms (2004)
PNAS 101, 12288-12293
   Abstract »    Full Text »    PDF »
CCAAT displacement protein/cut homolog recruits G9a histone lysine methyltransferase to repress transcription.
H. Nishio and M. J. Walsh (2004)
PNAS 101, 11257-11262
   Abstract »    Full Text »    PDF »
Reprogramming of a melanoma genome by nuclear transplantation.
K. Hochedlinger, R. Blelloch, C. Brennan, Y. Yamada, M. Kim, L. Chin, and R. Jaenisch (2004)
Genes & Dev. 18, 1875-1885
   Abstract »    Full Text »    PDF »
POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex.
J. Z.-S. Ye, D. Hockemeyer, A. N. Krutchinsky, D. Loayza, S. M. Hooper, B. T. Chait, and T. de Lange (2004)
Genes & Dev. 18, 1649-1654
   Abstract »    Full Text »    PDF »

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