![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
RESEARCH PAPER
-catenin activation and H3K4 methylation at Wnt target genes
1 Regulatory Biology Laboratory, The Salk Insitute for Biological Studies, La Jolla, California 92037, USA; 2 Department of Cancer and Cell Biology, Genomics Institute of the Novartis Research Foundation (GNF), San Diego, California 92121, USA
The APC tumor suppressor controls the stability and nuclear export of 
-catenin (-cat), a transcriptional coactivator of LEF-1/TCF HMG proteins in the Wnt/Wg signaling pathway. We show here that -cat and APC have opposing actions at Wnt target genes in vivo. The -cat C-terminal activation domain associates with TRRAP/TIP60 and mixed-lineage-leukemia (MLL1/MLL2) SET1-type chromatin-modifying complexes in vitro, and we show that -cat promotes H3K4 trimethylation at the c-Myc gene in vivo. H3K4 trimethylation in vivo requires prior ubiquitination of H2B, and we find that ubiquitin is necessary for transcription initiation on chromatin but not nonchromatin templates in vitro. Chromatin immunoprecipitation experiments reveal that -cat recruits Pygopus, Bcl-9/Legless, and MLL/SET1-type complexes to the c-Myc enhancer together with the negative Wnt regulators, APC, and TrCP. Interestingly, APC-mediated repression of c-Myc transcription in HT29-APC colorectal cancer cells is initiated by the transient binding of APC, TrCP, and the CtBP corepressor to the c-Myc enhancer, followed by stable binding of the TLE-1 and HDAC1 corepressors. Moreover, nuclear CtBP physically associates with full-length APC, but not with mutant SW480 or HT29 APC proteins. We conclude that, in addition to regulating the stability of -cat, APC facilitates CtBP-mediated repression of Wnt target genes in normal, but not in colorectal cancer cells.
[Keywords: Wnt signaling; -catenin; MLL1/MLL2/SET1; H3K4 methylation; APC tumor suppressor; CtBP; TrCP]
Received October 18, 2005; revised version accepted January 9, 2006.
3 These authors contributed equally to this work.
4 Corresponding author.
E-MAIL jones{at}salk.edu; FAX (858) 535-8194.
Related Article
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
-catenin inside the nucleus
Genes & Dev. 2006 20: 637-642.
This article has been cited by other articles:
|
|
 |
|
  Y. Wang, Y. Azuma, D. Moore, N. Osheroff, and K. L. Neufeld Interaction between Tumor Suppressor Adenomatous Polyposis Coli and Topoisomerase II{alpha}: Implication for the G2/M Transition Mol. Biol. Cell, October 1, 2008; 19(10): 4076 - 4085. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Grigoryan, P. Wend, A. Klaus, and W. Birchmeier Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of {beta}-catenin in mice Genes & Dev., September 1, 2008; 22(17): 2308 - 2341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Kouzmenko, K.-i. Takeyama, Y. Kawasaki, T. Akiyama, and S. Kato Ligand-dependent interaction between estrogen receptor alpha and adenomatous polyposis coli. Genes Cells, July 1, 2008; 13(7): 723 - 730. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Thompson, V. Tremblay, G. Lin, and D. A. Bochar CHD8 Is an ATP-Dependent Chromatin Remodeling Factor That Regulates {beta}-Catenin Target Genes Mol. Cell. Biol., June 15, 2008; 28(12): 3894 - 3904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sustmann, H. Flach, H. Ebert, Q. Eastman, and R. Grosschedl Cell-Type-Specific Function of BCL9 Involves a Transcriptional Activation Domain That Synergizes with {beta}-Catenin Mol. Cell. Biol., May 15, 2008; 28(10): 3526 - 3537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Hatzis, L. G. van der Flier, M. A. van Driel, V. Guryev, F. Nielsen, S. Denissov, I. J. Nijman, J. Koster, E. E. Santo, W. Welboren, et al. Genome-Wide Pattern of TCF7L2/TCF4 Chromatin Occupancy in Colorectal Cancer Cells Mol. Cell. Biol., April 15, 2008; 28(8): 2732 - 2744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-q. Gan, J.-y. Wang, Y. Xi, Z.-l. Wu, Y.-p. Li, and L. Li Nuclear Dvl, c-Jun, {beta}-catenin, and TCF form a complex leading to stabiLization of {beta}-catenin-TCF interaction J. Cell Biol., March 24, 2008; 180(6): 1087 - 1100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Zhu, M. B. Demay, and F. Gori Wdr5 Is Essential for Osteoblast Differentiation J. Biol. Chem., March 21, 2008; 283(12): 7361 - 7367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Parker, Y. Y. Ni, J. L. Chang, J. Li, and K. M. Cadigan Wingless Signaling Induces Widespread Chromatin Remodeling of Target Loci Mol. Cell. Biol., March 1, 2008; 28(5): 1815 - 1828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tran, F. Hamada, T. Schwarz-Romond, and M. Bienz Trabid, a new positive regulator of Wnt-induced transcription with preference for binding and cleaving K63-linked ubiquitin chains Genes & Dev., February 15, 2008; 22(4): 528 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Weiske, K. F. Albring, and O. Huber The tumor suppressor Fhit acts as a repressor of -catenin transcriptional activity PNAS, December 18, 2007; 104(51): 20344 - 20349. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wohrle, B. Wallmen, and A. Hecht Differential Control of Wnt Target Genes Involves Epigenetic Mechanisms and Selective Promoter Occupancy by T-Cell Factors Mol. Cell. Biol., December 1, 2007; 27(23): 8164 - 8177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kitagawa, W. J. Ray, H. Glantschnig, P. V. Nantermet, Y. Yu, C.-T. Leu, S.-i. Harada, S. Kato, and L. P. Freedman A Regulatory Circuit Mediating Convergence between Nurr1 Transcriptional Regulation and Wnt Signaling Mol. Cell. Biol., November 1, 2007; 27(21): 7486 - 7496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Daugherty and C. J. Gottardi Phospho-regulation of {beta}-Catenin Adhesion and Signaling Functions Physiology, October 1, 2007; 22(5): 303 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Aoki and M. M. Taketo Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene J. Cell Sci., October 1, 2007; 120(19): 3327 - 3335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-W. Cho, T. Hong, S. Hong, H. Guo, H. Yu, D. Kim, T. Guszczynski, G. R. Dressler, T. D. Copeland, M. Kalkum, et al. PTIP Associates with MLL3- and MLL4-containing Histone H3 Lysine 4 Methyltransferase Complex J. Biol. Chem., July 13, 2007; 282(28): 20395 - 20406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Tanny, H. Erdjument-Bromage, P. Tempst, and C. D. Allis Ubiquitylation of histone H2B controls RNA polymerase II transcription elongation independently of histone H3 methylation Genes & Dev., April 1, 2007; 21(7): 835 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Chen, C. K. Yang, M. Xia, C.-Y. Ou, and M. R. Stallcup Role of GAC63 in transcriptional activation mediated by {beta}-catenin Nucleic Acids Res., March 19, 2007; 35(6): 2084 - 2092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Schneikert and J. Behrens The canonical Wnt signalling pathway and its APC partner in colon cancer development Gut, March 1, 2007; 56(3): 417 - 425. [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Chao, W. M. Jones, and A. Bejsovec The HMG-box transcription factor SoxNeuro acts with Tcf to control Wg/Wnt signaling activity Development, March 1, 2007; 134(5): 989 - 997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Chen, W. A. Woodward, F. Behbod, S. Peddibhotla, M. P. Alfaro, T. A. Buchholz, and J. M. Rosen Wnt/beta-catenin mediates radiation resistance of Sca1+ progenitors in an immortalized mammary gland cell line J. Cell Sci., February 1, 2007; 120(3): 468 - 477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Schneikert, A. Grohmann, and J. Behrens Truncated APC regulates the transcriptional activity of {beta}-catenin in a cell cycle dependent manner Hum. Mol. Genet., January 15, 2007; 16(2): 199 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Yochum, R. Cleland, S. McWeeney, and R. H. Goodman An Antisense Transcript Induced by Wnt/beta-Catenin Signaling Decreases E2F4 J. Biol. Chem., January 12, 2007; 282(2): 871 - 878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. D. Nadauld, R. Phelps, B. C. Moore, A. Eisinger, I. T. Sandoval, S. Chidester, P. W. Peterson, E. J. Manos, B. Sklow, R. W. Burt, et al. Adenomatous Polyposis Coli Control of C-terminal Binding Protein-1 Stability Regulates Expression of Intestinal Retinol Dehydrogenases J. Biol. Chem., December 8, 2006; 281(49): 37828 - 37835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Iljin, M. Wolf, H. Edgren, S. Gupta, S. Kilpinen, R. I. Skotheim, M. Peltola, F. Smit, G. Verhaegh, J. Schalken, et al. TMPRSS2 Fusions with Oncogenic ETS Factors in Prostate Cancer Involve Unbalanced Genomic Rearrangements and Are Associated with HDAC1 and Epigenetic Reprogramming Cancer Res., November 1, 2006; 66(21): 10242 - 10246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lee, D.-K. Lee, Y. Dou, J. Lee, B. Lee, E. Kwak, Y.-Y. Kong, S.-K. Lee, R. G. Roeder, and J. W. Lee Coactivator as a target gene specificity determinant for histone H3 lysine 4 methyltransferases PNAS, October 17, 2006; 103(42): 15392 - 15397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. W.-H. Li, J.-H. T. Ting, N. N. Yokoyama, A. Bernstein, M. van de Wetering, and M. L. Waterman Wnt Activation and Alternative Promoter Repression of LEF1 in Colon Cancer. Mol. Cell. Biol., July 1, 2006; 26(14): 5284 - 5299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. He and J. D. Axelrod A WNTer wonderland in Snowbird. Development, July 1, 2006; 133(14): 2597 - 2603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Willert and K. A. Jones Wnt signaling: is the party in the nucleus? Genes & Dev., June 1, 2006; 20(11): 1394 - 1404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xiong and Y. Kotake No exit strategy? No problem: APC inhibits beta-catenin inside the nucleus. Genes & Dev., March 15, 2006; 20(6): 637 - 642. [Full Text] [PDF]
|
|
