Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

β-Catenin hits chromatin: regulation of Wnt target gene activation

Key Points

  • The canonical Wnt pathway fundamentally contributes to metazoan development, tissue homeostasis and human malignancies. At its core is the regulation of Wnt target gene transcription by nuclear β-catenin.

  • β-Catenin is one of the most prominent members of the Armadillo (ARM) repeat protein superfamily. To mediate Wnt target gene activation, the central region of the protein interacts with the DNA-binding T cell factor (TCF) family proteins that are bound to Wnt response elements (WREs), while the amino- and carboxy-terminal regions coordinate auxiliary chromatin remodelling and recognition cofactors.

  • The most N-terminal ARM repeat recruits BCL-9 (Legless (LGS) in Drosophila melanogaster), which in turn binds pygopus (Pygo). This interaction is required for all of the Wingless-dependent effects that have been analysed in D. melanogaster. Pygo has been implicated in the binding of modified histone H3 tails, thus linking its Wnt function with chromatin recognition.

  • Diverse chromatin-modifying factors are recruited by the more C-terminal region of β-catenin — the histone acetyltransferases (HATs) CBP, p300 and TIP60, the SWI/SNF factors BRG1 (Brahma (BRM) in D. melanogaster) and ISWI, the Mediator component MED12, and the polymerase-associated factor 1 (PAF1) complex protein parafibromin (Hyrax (HYX) in D. melanogaster). A simple paradigm is that the region of β-catenin from ARM repeat 11 to the C-terminal domain serves as a scaffold to orchestrate the recruitment and sequential exchange of chromatin-remodelling factors at WREs.

  • Is there crosstalk between the cofactors recruited to these N- and C-terminal tails of β-catenin? Several experimental readouts rely on the contribution of both sides. Furthermore, β-catenin-orchestrated chromatin remodelling could profoundly affect, and be co-dependent on, the activities of other transcription factors bound to a TCF-controlled genomic locus.

  • One of the key future challenges will be to elucidate how the activity of β-catenin can be curbed once it is engaged in gene activation. The known components of the nuclear Wnt signalling complex might contain an endogenous key for inactivating this process.

Abstract

The canonical Wnt pathway has gathered much attention in recent years owing to its fundamental contribution to metazoan development, tissue homeostasis and human malignancies. Wnt target gene transcription is regulated by nuclear β-catenin, and genetic assays have revealed various collaborating protein cofactors. Their daunting number and diverse nature, however, make it difficult to arrange an orderly picture of the nuclear Wnt transduction events. Yet, these findings emphasize that β-catenin-mediated transcription affects chromatin. How does β-catenin cope with chromatin regulation to turn on Wnt target genes?

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Theβ-catenin-dependent or canonical Wnt signalling pathway.
Figure 2: Nuclearβ-catenin interactions.
Figure 3: Sequential exchange of auxiliaryβ-catenin-binding factors at Wnt response elements.
Figure 4: Cooperative mechanism of TCF-occupied Wnt response elements.

Similar content being viewed by others

References

  1. Kohn, A. D. & Moon, R. T. Wnt and calcium signaling: β-catenin-independent pathways. Cell Calcium 38, 439–446 (2005).

    CAS  PubMed  Google Scholar 

  2. Clevers, H. Wnt/β-catenin signaling in development and disease. Cell 127, 469–480 (2006). An excellent review of the involvement and mechanisms of the entire Wnt signalling pathway in development and disease.

    CAS  PubMed  Google Scholar 

  3. Klaus, A. & Birchmeier, W. Wnt signalling and its impact on development and cancer. Nature Rev. Cancer 8, 387–398 (2008).

    CAS  Google Scholar 

  4. Bilic, J. et al. Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation. Science 316, 1619–1622 (2007).

    CAS  PubMed  Google Scholar 

  5. Huang, H. & He, X. Wnt/β-catenin signaling: new (and old) players and new insights. Curr. Opin. Cell Biol. 20, 119–125 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Henderson, B. R. & Fagotto, F. The ins and outs of APC and β-catenin nuclear transport. EMBO Rep. 3, 834–839 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Huber, A. H., Nelson, W. J. & Weis, W. I. Three-dimensional structure of the armadillo repeat region of β-catenin. Cell 90, 871–882 (1997).

    CAS  PubMed  Google Scholar 

  8. Xing, Y. et al. Crystal structure of a full-length β-catenin. Structure 16, 478–487 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Orsulic, S. & Peifer, M. An in vivo structure–function study of armadillo, the β-catenin homologue, reveals both separate and overlapping regions of the protein required for cell adhesion and for wingless signaling. J. Cell Biol. 134, 1283–1300 (1996). A seminal structure–function study carried out in D. melanogaster that yielded far-reaching insights into the function of β-catenin.

    CAS  PubMed  Google Scholar 

  10. Graham, T. A., Weaver, C., Mao, F., Kimelman, D. & Xu, W. Crystal structure of a β-catenin/Tcf complex. Cell 103, 885–896 (2000).

    CAS  PubMed  Google Scholar 

  11. Huber, A. H. & Weis, W. I. The structure of the β-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by β-catenin. Cell 105, 391–402 (2001).

    CAS  PubMed  Google Scholar 

  12. Brannon, M., Gomperts, M., Sumoy, L., Moon, R. T. & Kimelman, D. A β-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus. Genes Dev. 11, 2359–2370 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Cavallo, R. A. et al. Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature 395, 604–608 (1998).

    CAS  PubMed  Google Scholar 

  14. Roose, J. et al. The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature 395, 608–612 (1998).

    CAS  PubMed  Google Scholar 

  15. Brantjes, H., Roose, J., van De Wetering, M. & Clevers, H. All Tcf HMG box transcription factors interact with Groucho-related co-repressors. Nucleic Acids Res. 29, 1410–1419 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Courey, A. J. & Jia, S. Transcriptional repression: the long and the short of it. Genes Dev. 15, 2786–2796 (2001).

    CAS  PubMed  Google Scholar 

  17. Fang, M. et al. C-terminal-binding protein directly activates and represses Wnt transcriptional targets in Drosophila. EMBO J. 25, 2735–2745 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Daniels, D. L. & Weis, W. I. β-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation. Nature Struct. Mol. Biol. 12, 364–371 (2005).

    CAS  Google Scholar 

  19. Li, J. et al. CBP/p300 are bimodal regulators of Wnt signaling. EMBO J. 26, 2284–2294 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Parker, D. S., Ni, Y. Y., Chang, J. L., Li, J. & Cadigan, K. M. Wingless signaling induces widespread chromatin remodeling of target loci. Mol. Cell Biol. 28, 1815–1828 (2008).

    CAS  PubMed  Google Scholar 

  21. Hecht, A., Litterst, C. M., Huber, O. & Kemler, R. Functional characterization of multiple transactivating elements in β-catenin, some of which interact with the TATA-binding protein in vitro. J. Biol. Chem. 274, 18017–18025 (1999).

    CAS  PubMed  Google Scholar 

  22. Tutter, A. V., Fryer, C. J. & Jones, K. A. Chromatin-specific regulation of LEF-1-β-catenin transcription activation and inhibition in vitro. Genes Dev. 15, 3342–3354 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Eberharter, A. & Becker, P. B. Histone acetylation: a switch between repressive and permissive chromatin. EMBO Rep. 3, 224–229 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Narlikar, G. J., Fan, H. Y. & Kingston, R. E. Cooperation between complexes that regulate chromatin structure and transcription. Cell 108, 475–487 (2002). An extensive review that discusses histone acetylation and remodelling complexes, their interplay and their sequential recruitment to activated genes.

    CAS  PubMed  Google Scholar 

  25. Hecht, A., Vleminckx, K., Stemmler, M. P., van Roy, F. & Kemler, R. The p300/CBP acetyltransferases function as transcriptional coactivators of β-catenin in vertebrates. EMBO J. 19, 1839–1850 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Takemaru, K. I. & Moon, R. T. The transcriptional coactivator CBP interacts with β-catenin to activate gene expression. J. Cell Biol. 149, 249–254 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Ma, H., Nguyen, C., Lee, K. S. & Kahn, M. Differential roles for the coactivators CBP and p300 on TCF/β-catenin-mediated survivin gene expression. Oncogene 24, 3619–3631 (2005).

    CAS  PubMed  Google Scholar 

  28. Miyabayashi, T. et al. Wnt/β-catenin/CBP signaling maintains long-term murine embryonic stem cell pluripotency. Proc. Natl Acad. Sci. USA 104, 5668–5673 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Sierra, J., Yoshida, T., Joazeiro, C. A. & Jones, K. A. The APC tumor suppressor counteracts β-catenin activation and H3K4 methylation at Wnt target genes. Genes Dev. 20, 586–600 (2006). One of the first studies to apply time-course ChIP analysis to study the dynamics at a WRE.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Doyon, Y. & Cote, J. The highly conserved and multifunctional NuA4 HAT complex. Curr. Opin. Genet. Dev. 14, 147–154 (2004).

    CAS  PubMed  Google Scholar 

  31. Heintzman, N. D. et al. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nature Genet. 39, 311–318 (2007).

    CAS  PubMed  Google Scholar 

  32. Giese, K., Cox, J. & Grosschedl, R. The HMG domain of lymphoid enhancer factor 1 bends DNA and facilitates assembly of functional nucleoprotein structures. Cell 69, 185–195 (1992).

    CAS  PubMed  Google Scholar 

  33. Love, J. J. et al. Structural basis for DNA bending by the architectural transcription factor LEF-1. Nature 376, 791–795 (1995).

    CAS  PubMed  Google Scholar 

  34. Hatzis, P. et al. Genome-wide pattern of TCF7L2/TCF4 chromatin occupancy in colorectal cancer cells. Mol. Cell Biol. 28, 2732–2744 (2008). Information on TCF occupancy on a genomic level, such as binding site distribution at target gene loci and their structure.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Zlatanova, J., Seebart, C. & Tomschik, M. The linker-protein network: control of nucleosomal DNA accessibility. Trends Biochem. Sci. 33, 247–253 (2008).

    CAS  PubMed  Google Scholar 

  36. Racki, L. R. & Narlikar, G. J. ATP-dependent chromatin remodeling enzymes: two heads are not better, just different. Curr. Opin. Genet. Dev. 18, 137–144 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Kwon, C. S. & Wagner, D. Unwinding chromatin for development and growth: a few genes at a time. Trends Genet. 23, 403–412 (2007).

    CAS  PubMed  Google Scholar 

  38. Waltzer, L., Vandel, L. & Bienz, M. Teashirt is required for transcriptional repression mediated by high Wingless levels. EMBO J. 20, 137–145 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Deuring, R. et al. The ISWI chromatin-remodeling protein is required for gene expression and the maintenance of higher order chromatin structure in vivo. Mol. Cell 5, 355–365 (2000).

    CAS  PubMed  Google Scholar 

  40. Johnson, C. N., Adkins, N. L. & Georgel, P. Chromatin remodeling complexes: ATP-dependent machines in action. Biochem. Cell Biol. 83, 405–417 (2005).

    CAS  PubMed  Google Scholar 

  41. Liu, Y. I. et al. The chromatin remodelers ISWI and ACF1 directly repress Wingless transcriptional targets. Dev. Biol. 323, 41–52 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Shilatifard, A. Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation. Curr. Opin. Cell Biol. 20, 341–348 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Milne, T. A. et al. MLL associates specifically with a subset of transcriptionally active target genes. Proc. Natl Acad. Sci. USA 102, 14765–14770 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Slany, R. K. Chromatin control of gene expression: mixed-lineage leukemia methyltransferase SETs the stage for transcription. Proc. Natl Acad. Sci. USA 102, 14481–14482 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Shilatifard, A. Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu. Rev. Biochem. 75, 243–269 (2006). A good introduction to the mechanisms that underlie histone ubiquitylation and methylation, chromatin modification crosstalk and the catalysing protein complexes.

    CAS  PubMed  Google Scholar 

  46. Bray, S., Musisi, H. & Bienz, M. Bre1 is required for Notch signaling and histone modification. Dev. Cell 8, 279–286 (2005).

    CAS  PubMed  Google Scholar 

  47. Mosimann, C., Hausmann, G. & Basler, K. Parafibromin/Hyrax activates Wnt/Wg target gene transcription by direct association with β-catenin/Armadillo. Cell 125, 327–341 (2006).

    CAS  PubMed  Google Scholar 

  48. Iwata, T., Mizusawa, N., Taketani, Y., Itakura, M. & Yoshimoto, K. Parafibromin tumor suppressor enhances cell growth in the cells expressing SV40 large T antigen. Oncogene 26, 6176–6183 (2007).

    CAS  PubMed  Google Scholar 

  49. Sampietro, J. et al. Crystal structure of a β-catenin/BCL9/Tcf4 complex. Mol. Cell 24, 293–300 (2006).

    CAS  PubMed  Google Scholar 

  50. Thompson, B., Townsley, F., Rosin-Arbesfeld, R., Musisi, H. & Bienz, M. A new nuclear component of the Wnt signalling pathway. Nature Cell Biol. 4, 367–373 (2002).

    CAS  PubMed  Google Scholar 

  51. Parker, D. S., Jemison, J. & Cadigan, K. M. Pygopus, a nuclear PHD-finger protein required for Wingless signaling in Drosophila. Development 129, 2565–2576 (2002).

    CAS  PubMed  Google Scholar 

  52. Belenkaya, T. Y. et al. pygopus encodes a nuclear protein essential for wingless/Wnt signaling. Development 129, 4089–4101 (2002).

    CAS  PubMed  Google Scholar 

  53. Kramps, T. et al. Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear β-catenin–TCF complex. Cell 109, 47–60 (2002).

    CAS  PubMed  Google Scholar 

  54. Brembeck, F. H. et al. Essential role of BCL9-2 in the switch between β-catenin's adhesive and transcriptional functions. Genes Dev. 18, 2225–2230 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Sustmann, C., Flach, H., Ebert, H., Eastman, Q. & Grosschedl, R. Cell-type-specific function of BCL9 involves a transcriptional activation domain that synergizes with β-catenin. Mol. Cell. Biol. 28, 3526–3537 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Li, B. et al. Developmental phenotypes and reduced Wnt signaling in mice deficient for pygopus 2. Genesis 45, 318–325 (2007).

    CAS  PubMed  Google Scholar 

  57. Schwab, K. R. et al. Pygo1 and Pygo2 roles in Wnt signaling in mammalian kidney development. BMC Biol. 5, 15 (2007).

    PubMed  PubMed Central  Google Scholar 

  58. Song, N. et al. pygopus 2 has a crucial, Wnt pathway-independent function in lens induction. Development 134, 1873–1885 (2007).

    CAS  PubMed  Google Scholar 

  59. Nair, M. et al. Nuclear regulator Pygo2 controls spermiogenesis and histone H3 acetylation. Dev. Biol. 320, 446–455 (2008). References 56–59 describe the long-awaited and surprisingly mild loss-of 2011 function phenotypes of mammalian Pygo proteins.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Nakamura, Y. et al. Crystal structure analysis of the PHD domain of the transcription co-activator Pygopus. J. Mol. Biol. 370, 80–92 (2007).

    CAS  PubMed  Google Scholar 

  61. de la Roche, M. & Bienz, M. Wingless-independent association of Pygopus with dTCF target genes. Curr. Biol. 17, 556–561 (2007).

    CAS  PubMed  Google Scholar 

  62. Townsley, F. M., Cliffe, A. & Bienz, M. Pygopus and Legless target Armadillo/β-catenin to the nucleus to enable its transcriptional co-activator function. Nature Cell Biol. 6, 626–633 (2004).

    CAS  PubMed  Google Scholar 

  63. Hoffmans, R., Städeli, R. & Basler, K. Pygopus and legless provide essential transcriptional coactivator functions to armadillo/β-catenin. Curr. Biol. 15, 1207–1211 (2005).

    CAS  PubMed  Google Scholar 

  64. Green, K. A. & Carroll, J. S. Oestrogen-receptor-mediated transcription and the influence of co-factors and chromatin state. Nature Rev. Cancer 7, 713–722 (2007).

    CAS  PubMed  Google Scholar 

  65. Li, J. & Wang, C. Y. TBL1–TBLR1 and β-catenin recruit each other to Wnt target-gene promoter for transcription activation and oncogenesis. Nature Cell Biol. 10, 160–169 (2008).

    CAS  PubMed  Google Scholar 

  66. Mellor, J. It takes a PHD to read the histone code. Cell 126, 22–24 (2006).

    CAS  PubMed  Google Scholar 

  67. Bienz, M. The PHD finger, a nuclear protein-interaction domain. Trends Biochem. Sci. 31, 35–40 (2006).

    CAS  PubMed  Google Scholar 

  68. Fiedler, M. et al. Decoding of methylated histone H3 tail by the Pygo–BCL9 Wnt signaling complex. Mol. Cell 30, 507–518 (2008). Seminal study of the Pygo PHD structure, which implicates, for the first time, this particular domain in histone H3 binding.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Lewis, B. A. & Reinberg, D. The mediator coactivator complex: functional and physical roles in transcriptional regulation. J. Cell Sci. 116, 3667–3675 (2003).

    CAS  PubMed  Google Scholar 

  70. Kornberg, R. D. Mediator and the mechanism of transcriptional activation. Trends Biochem. Sci. 30, 235–239 (2005).

    CAS  PubMed  Google Scholar 

  71. Malik, S. & Roeder, R. G. Dynamic regulation of pol II transcription by the mammalian Mediator complex. Trends Biochem. Sci. 30, 256–263 (2005).

    CAS  PubMed  Google Scholar 

  72. Kim, S., Xu, X., Hecht, A. & Boyer, T. G. Mediator is a transducer of Wnt/β-catenin signaling. J. Biol. Chem. 281, 14066–14075 (2006).

    CAS  PubMed  Google Scholar 

  73. Lin, X., Rinaldo, L., Fazly, A. F. & Xu, X. Depletion of Med10 enhances Wnt and suppresses Nodal signaling during zebrafish embryogenesis. Dev. Biol. 303, 536–548 (2007).

    CAS  PubMed  Google Scholar 

  74. Carrera, I., Janody, F., Leeds, N., Duveau, F. & Treisman, J. E. Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13. Proc. Natl Acad. Sci. USA 105, 6644–6649 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Städeli, R. & Basler, K. Dissecting nuclear Wingless signalling: recruitment of the transcriptional co-activator Pygopus by a chain of adaptor proteins. Mech. Dev. 122, 1171–1182 (2005).

    PubMed  Google Scholar 

  76. Bauer, A., Huber, O. & Kemler, R. Pontin52, an interaction partner of β-catenin, binds to the TATA box binding protein. Proc. Natl Acad. Sci. USA 95, 14787–14792 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Feng, Y., Lee, N. & Fearon, E. R. TIP49 regulates β-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res. 63, 8726–8734 (2003).

    CAS  PubMed  Google Scholar 

  78. Kim, J. H. et al. Transcriptional regulation of a metastasis suppressor gene by Tip60 and β-catenin complexes. Nature 434, 921–926 (2005).

    CAS  PubMed  Google Scholar 

  79. Yoon, S., Qiu, H., Swanson, M. J. & Hinnebusch, A. G. Recruitment of SWI/SNF by Gcn4p does not require Snf2p or Gcn5p but depends strongly on SWI/SNF integrity, SRB mediator, and SAGA. Mol. Cell. Biol. 23, 8829–8845 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Roeder, R. G. Transcriptional regulation and the role of diverse coactivators in animal cells. FEBS Lett. 579, 909–915 (2005). A comprehensive review of how transcription factors use their auxiliary cofactors to achieve transcriptional activation.

    CAS  PubMed  Google Scholar 

  81. Fry, C. J. & Peterson, C. L. Chromatin remodeling enzymes: who's on first? Curr. Biol. 11, R185–R197 (2001).

    CAS  PubMed  Google Scholar 

  82. Nishita, M. et al. Interaction between Wnt and TGF-β signalling pathways during formation of Spemann's organizer. Nature 403, 781–785 (2000).

    CAS  PubMed  Google Scholar 

  83. Blauwkamp, T. A., Chang, M. V. & Cadigan, K. M. Novel TCF-binding sites specify transcriptional repression by Wnt signalling. EMBO J. 27, 1436–1446 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Yang, F. et al. Linking β-catenin to androgen-signaling pathway. J. Biol. Chem. 277, 11336–11344 (2002).

    CAS  PubMed  Google Scholar 

  85. Sinner, D., Rankin, S., Lee, M. & Zorn, A. M. Sox17 and β-catenin cooperate to regulate the transcription of endodermal genes. Development 131, 3069–3080 (2004).

    CAS  PubMed  Google Scholar 

  86. Neufeld, K. L., Zhang, F., Cullen, B. R. & White, R. L. APC-mediated downregulation of β-catenin activity involves nuclear sequestration and nuclear export. EMBO Rep. 1, 519–523 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Cong, F. & Varmus, H. Nuclear–cytoplasmic shuttling of Axin regulates subcellular localization of β-catenin. Proc. Natl Acad. Sci. USA 101, 2882–2887 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Thompson, B. A., Tremblay, V., Lin, G. & Bochar, D. A. CHD8 is an ATP-dependent chromatin remodeling factor that regulates β-catenin target genes. Mol. Cell. Biol. 28, 3894–3904 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Mieszczanek, J., de la Roche, M. & Bienz, M. A role of Pygopus as an anti-repressor in facilitating Wnt-dependent transcription. Proc. Natl Acad. Sci. USA 105, 19324–19329 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Wang, S. & Jones, K. A. CK2 controls the recruitment of Wnt regulators to target genes in vivo. Curr. Biol. 16, 2239–2244 (2006).

    CAS  PubMed  Google Scholar 

  91. Willert, K. & Jones, K. A. Wnt signaling: is the party in the nucleus? Genes Dev. 20, 1394–1404 (2006).

    CAS  PubMed  Google Scholar 

  92. Krogan, N. J. et al. RNA polymerase II elongation factors of Saccharomyces cerevisiae: a targeted proteomics approach. Mol. Cell. Biol. 22, 6979–6992 (2002).

    CAS  Google Scholar 

  93. Barker, N. et al. The chromatin remodelling factor Brg-1 interacts with β-catenin to promote target gene activation. EMBO J. 20, 4935–4943 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Fry, D. C. Protein–protein interactions as targets for small molecule drug discovery. Biopolymers 84, 535–552 (2006).

    CAS  PubMed  Google Scholar 

  95. Major, M. B. et al. New regulators of Wnt/β-catenin signaling revealed by integrative molecular screening. Sci. Signal. 1, ra12 (2008).

    PubMed  Google Scholar 

  96. van de Wetering, M., Oosterwegel, M., Dooijes, D. & Clevers, H. Identification and cloning of TCF-1, a T lymphocyte-specific transcription factor containing a sequence-specific HMG box. EMBO J. 10, 123–132 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Korinek, V. et al. Constitutive transcriptional activation by a β-catenin–Tcf complex in APC−/− colon carcinoma. Science 275, 1784–1787 (1997).

    CAS  PubMed  Google Scholar 

  98. Barolo, S. Transgenic Wnt/TCF pathway reporters: all you need is Lef? Oncogene 25, 7505–7511 (2006). Discusses the fidelity and quality of the various transgenic Wnt–β-catenin–TCF reporters and compares their in vivo transcriptional responses with those of natural Wnt target genes.

    CAS  PubMed  Google Scholar 

  99. Sansom, O. J. et al. Cyclin D1 is not an immediate target of β-catenin following Apc loss in the intestine. J. Biol. Chem. 280, 28463–28467 (2005).

    CAS  PubMed  Google Scholar 

  100. Jho, E. H. et al. Wnt/β-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol. Cell. Biol. 22, 1172–1183 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We apologize to those colleagues whose work we do not directly cite owing to space limitations. We would also like to thank past and present members of the Basler laboratory for creating an environment that nurtured the ideas presented in this Review. This work was supported by the National Center of Competence in Research “Frontiers in Genetics,” the Swiss National Science Foundation, and the Kanton of Zürich.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Konrad Basler.

Related links

Related links

DATABASES

Interpro

HMG

SET

FURTHER INFORMATION

Konrad Basler's homepage

Wnt homepage

Glossary

Nucleosome

An assembly of 146 base pairs of DNA wrapped in 2 turns around an octameric complex that is composed of the core histones H2A, H2B, H3 and H4, thus forming the basic unit of chromatin.

Enhanceosome

Describes the cooperative protein assembly that is formed at a transcription-controlling enhancer region. The enhanceosome involves gene-specific transcription factors, chromatin-remodelling factors and components of the general transcription machinery.

MLL complex

(Mixed lineage leukaemia). A COMPASS (complex proteins associated with Set1)-like complex with histone methyltransferase activity, which is minimally composed of MLL, ASH2, menin, RBBP5, WDR5 and DPY30.

Histone methyltransferase

An enzyme that catalyses the transfer of a methyl group from S-adenosylmethionine to Lys or Arg residues found in histones.

PAF1 complex

(Polymerase-associated factor 1). A protein assembly that mediates histone modifications during initiation and elongation, minimally containing the factors PAF1, CTR9, LEO1, RTF1 and CDC73.

Polytene chromosome

A large chromosome that results from the successive replication of a homologous chromosome, without ensuing separation and cell division.

Pre-initiation complex

Formed minimally by the general transcription factors TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH, this complex positions RNA polymerase II and prepares the necessary steps required for transcriptional initiation.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mosimann, C., Hausmann, G. & Basler, K. β-Catenin hits chromatin: regulation of Wnt target gene activation. Nat Rev Mol Cell Biol 10, 276–286 (2009). https://doi.org/10.1038/nrm2654

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm2654

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing