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A Transcriptional Switch Mediated by Cofactor Methylation
Wei Xu,1Hongwu Chen,2Keyong Du,3Hiroshi Asahara,3Marc Tini,1Beverly M. Emerson,4Marc Montminy,3Ronald M. Evans15*
We describe a molecular switch based on the controlled methylation
of nucleosome and the transcriptional cofactors, the CREB-bindingproteins (CBP)/p300. The CBP/p300 methylation site is localizedto an
arginine residue that is essential for stabilizing the structureof the
KIX domain, which mediates CREB recruitment. Methylationof KIX by
coactivator-associated arginine methyltransferase 1(CARM1) blocks CREB
activation by disabling the interaction betweenKIX and the kinase
inducible domain (KID) of CREB. Thus, CARM1functions as a corepressor
in cyclic adenosine monophosphate signalingpathway via its
methyltransferase activity while acting as a coactivatorfor nuclear
hormones. These results provide strong in vivo andin vitro evidence
that histone methylation plays a key role inhormone-induced gene
activation and define cofactor methylationas a new regulatory
mechanism in hormone signaling.
1 Gene Expression Laboratory,
2 Department of Biological Chemistry, University of
California Davis Cancer Center/Basic Science, Sacramento, CA 95817, USA.
3 Peptide Biology Laboratory,
4 Regulatory Biology Laboratory, The Salk Institute
for Biological Studies, La Jolla, CA 92037, USA.
5 Howard Hughes Medical Institute, La Jolla, CA
92037, USA.
*
To whom correspondence should be addressed. E-mail:
evans{at}salk.edu
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PERSPECTIVES
Kenichi Nishioka and Danny Reinberg (21 December 2001) Science294 (5551), 2497.
[DOI: 10.1126/science.1067622] |Summary »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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278, 45340-45351
|Abstract »|Full Text »|PDF »
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278, 39402-39412
|Abstract »|Full Text »|PDF »
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K. Hosohata, P. Li, Y. Hosohata, J. Qin, R. G. Roeder, and Z. Wang (2003)
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23, 7019-7029
|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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23, 3456-3467
|Abstract »|Full Text »|PDF »
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U. Kuhn, A. Nemeth, S. Meyer, and E. Wahle (2003)
J. Biol. Chem.
278, 16916-16925
|Abstract »|Full Text »|PDF »
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P. M. Sadow, E. Koo, O. Chassande, K. Gauthier, J. Samarut, J. Xu, B. W. O'Malley, H. Seo, Y. Murata, and R. E. Weiss (2003)
Mol. Endocrinol.
17, 882-894
|Abstract »|Full Text »|PDF »
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K. Tenbrock, Y.-T. Juang, M. Tolnay, and G. C. Tsokos (2003)
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170, 2971-2976
|Abstract »|Full Text »|PDF »
Androgen-induced recruitment of RNA polymerase II to a nuclear receptor-p160 coactivator complex.
M. C. Louie, H. Q. Yang, A.-H. Ma, W. Xu, J. X. Zou, H.-J. Kung, and H.-W. Chen (2003)
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100, 2226-2230
|Abstract »|Full Text »|PDF »
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F.-M. Boisvert, J. Cote, M.-C. Boulanger, P. Cleroux, F. Bachand, C. Autexier, and S. Richard (2002)
J. Cell Biol.
159, 957-969
|Abstract »|Full Text »|PDF »
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V. Christiaens, C. L. Bevan, L. Callewaert, A. Haelens, G. Verrijdt, W. Rombauts, and F. Claessens (2002)
J. Biol. Chem.
277, 49230-49237
|Abstract »|Full Text »|PDF »
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P. Misra, E. D. Owuor, W. Li, S. Yu, C. Qi, K. Meyer, Y.-J. Zhu, M. S. Rao, A.-N. T. Kong, and J. K. Reddy (2002)
J. Biol. Chem.
277, 48745-48754
|Abstract »|Full Text »|PDF »
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C. Teyssier, D. Chen, and M. R. Stallcup (2002)
J. Biol. Chem.
277, 46066-46072
|Abstract »|Full Text »|PDF »
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H. Li, S. Park, B. Kilburn, M. A. Jelinek, A. Henschen-Edman, D. W. Aswad, M. R. Stallcup, and I. A. Laird-Offringa (2002)
J. Biol. Chem.
277, 44623-44630
|Abstract »|Full Text »|PDF »
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S. Surapureddi, S. Yu, H. Bu, T. Hashimoto, A. V. Yeldandi, P. Kashireddy, M. Cherkaoui-Malki, C. Qi, Y.-J. Zhu, M. S. Rao, et al. (2002)
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99, 11836-11841
|Abstract »|Full Text »|PDF »
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C. Qi, J. Chang, Y. Zhu, A. V. Yeldandi, S. M. Rao, and Y.-J. Zhu (2002)
J. Biol. Chem.
277, 28624-28630
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M. Tachibana, K. Sugimoto, M. Nozaki, J. Ueda, T. Ohta, M. Ohki, M. Fukuda, N. Takeda, H. Niida, H. Kato, et al. (2002)
Genes & Dev.
16, 1779-1791
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H. H. Ng, Q. Feng, H. Wang, H. Erdjument-Bromage, P. Tempst, Y. Zhang, and K. Struhl (2002)
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16, 1518-1527
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J. Biol. Chem.
277, 20011-20019
|Abstract »|Full Text »|PDF »
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K. Nishioka, S. Chuikov, K. Sarma, H. Erdjument-Bromage, C. D. Allis, P. Tempst, and D. Reinberg (2002)
Genes & Dev.
16, 479-489
|Abstract »|Full Text »|PDF »
