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Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia

Nature Chemical Biology volume 11, pages 571–578 (2015)Cite this article

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An Erratum to this article was published on 17 September 2015

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Abstract

The CEBPA gene is mutated in 9% of patients with acute myeloid leukemia (AML). Selective expression of a short (30-kDa) CCAAT-enhancer binding protein-α (C/EBPα) translational isoform, termed p30, represents the most common type of CEBPA mutation in AML. The molecular mechanisms underlying p30-mediated transformation remain incompletely understood. We show that C/EBPα p30, but not the normal p42 isoform, preferentially interacts with Wdr5, a key component of SET/MLL (SET-domain/mixed-lineage leukemia) histone-methyltransferase complexes. Accordingly, p30-bound genomic regions were enriched for MLL-dependent H3K4me3 marks. The p30-dependent increase in self-renewal and inhibition of myeloid differentiation required Wdr5, as downregulation of the latter inhibited proliferation and restored differentiation in p30-dependent AML models. OICR-9429 is a new small-molecule antagonist of the Wdr5-MLL interaction. This compound selectively inhibited proliferation and induced differentiation in p30-expressing human AML cells. Our data reveal the mechanism of p30-dependent transformation and establish the essential p30 cofactor Wdr5 as a therapeutic target in CEBPA-mutant AML.

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Figure 1: C/EBPα p30 preferably interacts with Wdr5 and the SET/MLL HMT complex, leading to increased colocalization of p30 and H3K4me3 on chromatin.
Figure 2: Loss of Wdr5 restores granulocytic differentiation potential in C/EBPα p30-expressing cells.
Figure 3: Wdr5 is required to maintain C/EBPα p30-dependent self-renewal in vitro and in vivo.
Figure 4: OICR-9429 binds WDR5 in the MLL WIN motif-binding pocket.
Figure 5: OICR-9429 is a small-molecule antagonist of the Wdr5-MLL interaction.
Figure 6: Pharmacological antagonism of the WDR5-MLL interaction by OICR-9429 selectively affects p30-expressing cells.

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  • 20 August 2015

    In the author list, affiliation and correspondence information for Cheryl Arrowsmith was missing. Her name should be accompanied by affiliation number 3 (signifying the Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada) and by an asterisk indicating her status as a corresponding author. These errors have been corrected in the HTML and PDF versions of the article.

References

  1. Koschmieder, S., Halmos, B., Levantini, E. & Tenen, D.G. Dysregulation of the C/EBPα differentiation pathway in human cancer. J. Clin. Oncol. 27, 619–628 (2009).

    CAS  PubMed  Google Scholar 

  2. Zhang, P. et al. Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBPα. Immunity 21, 853–863 (2004).

    CAS  PubMed  Google Scholar 

  3. Leroy, H. et al. CEBPA point mutations in hematological malignancies. Leukemia 19, 329–334 (2005).

    CAS  PubMed  Google Scholar 

  4. Fasan, A. et al. The role of different genetic subtypes of CEBPA mutated AML. Leukemia 28, 794–803 (2014).

    CAS  PubMed  Google Scholar 

  5. Nerlov, C. C/EBPα mutations in acute myeloid leukaemias. Nat. Rev. Cancer 4, 394–400 (2004).

    CAS  PubMed  Google Scholar 

  6. Kirstetter, P. et al. Modeling of C/EBPα mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells. Cancer Cell 13, 299–310 (2008).

    CAS  PubMed  Google Scholar 

  7. Friedman, A.D. & McKnight, S. Identification of two polypeptide segments of CCAAT/enhancer-binding protein required for transcriptional activation of the serum albumin gene. Genes Dev. 4, 1416–1426 (1990).

    CAS  PubMed  Google Scholar 

  8. Nerlov, C. & Ziff, E.B. Three levels of functional interaction determine the activity of CCAAT/enhancer binding protein-α on the serum albumin promoter. Genes Dev. 8, 350–362 (1994).

    CAS  PubMed  Google Scholar 

  9. Pedersen, T.A., Kowenz-Leutz, E., Leutz, A. & Nerlov, C. Cooperation between C/EBPα TBP/TFIIB and SWI/SNF recruiting domains is required for adipocyte differentiation. Genes Dev. 15, 3208–3216 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Slomiany, B.A., Arigo, K.L.D., Kelly, M.M. & Kurtz, D.T. C/EBPα inhibits cell growth via direct repression of E2F-DP–mediated transcription. Mol. Cell. Biol. 20, 5986–5997 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Porse, B.T. et al. E2F repression by C/EBPα is required for adipogenesis and granulopoiesis in vivo. Cell 107, 247–258 (2001).

    CAS  PubMed  Google Scholar 

  12. D'Alo', F. et al. The amino terminal and E2F interaction domains are critical for C/EBPα–mediated induction of granulopoietic development of hematopoietic cells. Blood 102, 3163–3171 (2003).

    CAS  PubMed  Google Scholar 

  13. Wang, Q.-F., Cleaves, R., Kummalue, T., Nerlov, C. & Friedman, A.D. Cell cycle inhibition mediated by the outer surface of the C/EBPα basic region is required but not sufficient for granulopoiesis. Oncogene 22, 2548–2557 (2003).

    CAS  PubMed  Google Scholar 

  14. Cleaves, R., Wang, Q. & Friedman, A.D. C/EBPα p30, a myeloid leukemia oncoprotein, limits G-CSF receptor expression but not terminal granulopoiesis via site-selective inhibition of C/EBP DNA binding. Oncogene 23, 716–725 (2004).

    CAS  PubMed  Google Scholar 

  15. Zada, A.A. et al. Proteomic discovery of Max as a novel interacting partner of C/EBPα: a Myc/Max/Mad link. Leukemia 20, 2137–2146 (2006).

    CAS  PubMed  Google Scholar 

  16. Trivedi, A.K. et al. Proteomic identification of C/EBP-DBD multiprotein complex: JNK1 activates stem cell regulator C/EBPα by inhibiting its ubiquitination. Oncogene 26, 1789–1801 (2007).

    CAS  PubMed  Google Scholar 

  17. Bararia, D. et al. Proteomic identification of the MYST domain histone acetyltransferase TIP60 (HTATIP) as a co-activator of the myeloid transcription factor C/EBPα. Leukemia 22, 800–807 (2008).

    CAS  PubMed  Google Scholar 

  18. Koleva, R.I. et al. C/EBPα and DEK coordinately regulate myeloid differentiation. Blood 119, 4878–4888 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Fujimoto, T., Anderson, K., Jacobsen, S.E.W., Nishikawa, S.-I. & Nerlov, C. Cdk6 blocks myeloid differentiation by interfering with Runx1 DNA binding and Runx1-C/EBPα interaction. EMBO J. 26, 2361–2370 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Wysocka, J. et al. WDR5 associates with histone H3 methylated at K4 and is essential for H3K4 methylation and vertebrate development. Cell 121, 859–872 (2005).

    CAS  PubMed  Google Scholar 

  21. Bolshan, Y. et al. Synthesis, optimization, and evaluation of novel small molecules as antagonists of WDR5-MLL interaction. ACS Med. Chem. Lett. 4, 353–357 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Senisterra, G. et al. Small-molecule inhibition of MLL activity by disruption of its interaction with WDR5. Biochem. J. 449, 151–159 (2013).

    CAS  PubMed  Google Scholar 

  23. Migliori, V. et al. Symmetric dimethylation of H3R2 is a newly identified histone mark that supports euchromatin maintenance. Nat. Struct. Mol. Biol. 19, 136–144 (2012).

    CAS  PubMed  Google Scholar 

  24. Dias, J. et al. Structural analysis of the KANSL1/WDR5/KANSL2 complex reveals that WDR5 is required for efficient assembly and chromatin targeting of the NSL complex. Genes Dev. 28, 929–942 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide. Proc. Natl. Acad. Sci. USA 102, 15545–15550 (2005).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Dou, Y. et al. Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nat. Struct. Mol. Biol. 13, 713–719 (2006).

    CAS  PubMed  Google Scholar 

  27. Couture, J.-F., Collazo, E. & Trievel, R.C. Molecular recognition of histone H3 by the WD40 protein WDR5. Nat. Struct. Mol. Biol. 13, 698–703 (2006).

    CAS  PubMed  Google Scholar 

  28. Song, J.-J. & Kingston, R.E. WDR5 interacts with mixed lineage leukemia (MLL) protein via the histone H3-binding pocket. J. Biol. Chem. 283, 35258–35264 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Patel, A., Dharmarajan, V. & Cosgrove, M.S. Structure of WDR5 bound to mixed lineage leukemia protein-1 peptide. J. Biol. Chem. 283, 32158–32161 (2008).

    CAS  PubMed  Google Scholar 

  30. Ruthenburg, A.J. et al. Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex. Nat. Struct. Mol. Biol. 13, 704–712 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Ang, Y.-S. et al. Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network. Cell 145, 183–197 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Yu, M. et al. Insights into GATA-1–mediated gene activation versus repression via genome-wide chromatin occupancy analysis. Mol. Cell 36, 682–695 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Dou, Y. et al. Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. Cell 121, 873–885 (2005).

    Article  CAS  PubMed  Google Scholar 

  34. Tyagi, S., Chabes, A.L., Wysocka, J. & Herr, W. E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases. Mol. Cell 27, 107–119 (2007).

    CAS  PubMed  Google Scholar 

  35. Cao, F. et al. Targeting MLL1 H3K4 methyltransferase activity in mixed-lineage leukemia. Mol. Cell 53, 247–261 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Lavallée-Adam, M., Cloutier, P., Coulombe, B. & Blanchette, M. Modeling contaminants in AP-MS/MS experiments. J. Proteome Res. 10, 886–895 (2011).

    PubMed  Google Scholar 

  37. Zuber, J. et al. Toolkit for evaluating genes required for proliferation and survival using tetracycline-regulated RNAi. Nat. Biotechnol. 29, 79–83 (2011).

    CAS  PubMed  Google Scholar 

  38. Shevchenko, A., Wilm, M., Vorm, O. & Mann, M. Mass spectrometric sequencing of proteins from silver-stained polyacrylamide gels. Anal. Chem. 68, 850–858 (1996).

    CAS  PubMed  Google Scholar 

  39. Bennett, K.L. et al. Proteomic analysis of human cataract aqueous humour: Comparison of one-dimensional gel LCMS with two-dimensional LCMS of unlabelled and iTRAQ-labelled specimens. J. Proteomics 74, 151–166 (2011).

    CAS  PubMed  Google Scholar 

  40. Olsen, J.V. et al. Parts per million mass accuracy on an Orbitrap mass spectrometer via lock mass injection into a C-trap. Mol. Cell. Proteomics 4, 2010–2021 (2005).

    CAS  PubMed  Google Scholar 

  41. Colinge, J., Masselot, A., Giron, M., Dessigny, T. & Magnin, J. OLAV: towards high-throughput tandem mass spectrometry data identification. Proteomics 3, 1454–1463 (2003).

    CAS  PubMed  Google Scholar 

  42. Huber, K.V. et al. Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy. Nature 508, 222–227 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in Os. Meth. Enzymol. 276, 307–326 (1997).

    CAS  Google Scholar 

  44. McCoy, A.J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658–674 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Schüttelkopf, A.W. & van Aalten, D.M.F. PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr. D Biol. Crystallogr. 60, 1355–1363 (2004).

    Article  PubMed  Google Scholar 

  46. Murshudov, G.N., Vagin, A.A. & Dodson, E.J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D Biol. Crystallogr. 53, 240–255 (1997).

    Article  CAS  PubMed  Google Scholar 

  47. Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126–2132 (2004).

    PubMed  Google Scholar 

  48. Davis, I.W., Murray, L.W., Richardson, J.S. & Richardson, D.C. MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes. Nucleic Acids Res. 32, W615–W619 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Siarheyeva, A. et al. An allosteric inhibitor of protein arginine methyltransferase 3. Structure 20, 1425–1435 (2012).

    CAS  PubMed  Google Scholar 

  50. Yu, W. et al. Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors. Nat. Commun. 3, 1288 (2012).

    PubMed  Google Scholar 

  51. Niesen, F.H., Berglund, H. & Vedadi, M. The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat. Protoc. 2, 2212–2221 (2007).

    CAS  PubMed  Google Scholar 

  52. Langmead, B. & Salzberg, S.L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Zhang, Y. et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9, R137 (2008).

    PubMed  PubMed Central  Google Scholar 

  54. Feng, J., Liu, T., Qin, B., Zhang, Y. & Liu, X.S. Identifying ChIP-seq enrichment using MACS. Nat. Protoc. 7, 1728–1740 (2012).

    CAS  PubMed  Google Scholar 

  55. Salmon-Divon, M., Dvinge, H., Tammoja, K. & Bertone, P. PeakAnalyzer: genome-wide annotation of chromatin binding and modification loci. BMC Bioinformatics 11, 415 (2010).

    PubMed  PubMed Central  Google Scholar 

  56. Astapova, I. et al. The nuclear corepressor, NCoR, regulates thyroid hormone action in vivo. Proc. Natl. Acad. Sci. USA 105, 19544–19549 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Irizarry, R.A. et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4, 249–264 (2003).

    PubMed  Google Scholar 

  58. Bilban, M. et al. Deregulated expression of fat and muscle genes in B-cell chronic lymphocytic leukemia with high lipoprotein lipase expression. Leukemia 20, 1080–1088 (2006).

    CAS  PubMed  Google Scholar 

  59. Schmittgen, T.D. & Livak, K.J. Analyzing real-time PCR data by the comparative CT method. Nat. Protoc. 3, 1101–1108 (2008).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank M. Gridling, M. Planyavsky, D. Printz and A. Spittler for experimental help and K. Kandasamy and M. Schuster for bioinformatic help. Next-generation sequencing was performed at the Campus Science Support Facilities Next-Generation Sequencing Unit (http://www.csf.ac.at/). F.G. and R.G. were funded by the Austrian Science Fund (FWF grant P22282-B11). A. Skucha is supported by FP7-PEOPLE-2011-ITN Project HemID (289611). The Superti-Furga laboratory is supported by the Austrian Academy of Sciences and by European Research Council (ERC) grant ERC-2009-AdG-250179-i-FIVE. The Structural Genomics Consortium is a registered charity (no. 1097737) that receives funds from AbbVie, Bayer, Boehringer Ingelheim, Genome Canada through the Ontario Genomics Institute (OGI-055), GlaxoSmithKline, Janssen, Lilly Canada, the Novartis Research Foundation, the Ontario Ministry of Economic Development and Innovation, Pfizer, Takeda and the Wellcome Trust (092809/Z/10/Z). The Ontario Institute for Cancer Research is funded by the Government of Ontario. Funding was also provided by the Leukemia and Lymphoma Society of Canada.

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Author notes

  1. Florian Grebien, Masoud Vedadi, Matthäus Getlik, Cheryl H Arrowsmith and Giulio Superti-Furga: These authors contributed equally to this work.

Authors and Affiliations

  1. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria

    Florian Grebien, Roberto Giambruno, Anna Skucha, Sarah Vittori, Alexey Stukalov, Kilian V M Huber, Andreas Schönegger, Christoph Bock, Keiryn L Bennett & Giulio Superti-Furga

  2. Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria

    Florian Grebien

  3. Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada

    Masoud Vedadi, Ekaterina Kuznetsova, David Smil, Dalia Barsyte-Lovejoy, Fengling Li, Matthieu Schapira, Hong Wu, Aiping Dong, Guillermo Senisterra, Peter J Brown & Cheryl H Arrowsmith

  4. Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada

    Masoud Vedadi, Matthieu Schapira & Rima Al-awar

  5. Drug Discovery Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada

    Matthäus Getlik, Gennadiy Poda, Richard Marcellus & Rima Al-awar

  6. MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK

    Amit Grover & Claus Nerlov

  7. Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands

    Roberto Avellino & Ruud Delwel

  8. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada

    Gennadiy Poda

  9. Department of Laboratory Medicine and Core Facility Genomics, Core Facilities, Medical University Vienna, Vienna, Austria

    Martin Bilban

  10. Research Institute of Molecular Pathology, Vienna, Austria

    Johannes Zuber

  11. Princess Margaret Cancer Centre, Toronto, Ontario, Canada

    Cheryl H Arrowsmith

  12. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

    Cheryl H Arrowsmith

  13. Center for Physiology and Pharmacology, Medical University Vienna, Vienna, Austria

    Giulio Superti-Furga

Authors
  1. Florian Grebien
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  31. Giulio Superti-Furga
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Contributions

F.G., M.V., R.G., A.G., R.A., A. Skucha, S.V., E.K., D.B.-L., F.L, G.S., K.V.M.H. and R.M. planned, performed and analyzed biochemical, biophysical, cellular and in vivo experiments. M.G., D.S., G.P., M.S., P.J.B. and R.A. contributed to chemical design and synthesis of OICR-9429 and OICR-0547. H.W., A.D. and M.S. solved and analyzed the X-ray crystal structure of WDR5 in complex with OICR-9429. A. Stukalov, A. Schönegger, M.B. and C.B. performed bioinformatic analyses. J.Z., K.L.B., R.D. and C.N. provided access to vital tools and technologies, planned experiments and analyzed results. F.G., M.V., P.J.B., R.A., C.H.A. and G.S.-F. designed the study, planned experiments, analyzed results and wrote the paper.

Corresponding authors

Correspondence to Florian Grebien, Cheryl H Arrowsmith or Giulio Superti-Furga.

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Grebien, F., Vedadi, M., Getlik, M. et al. Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia. Nat Chem Biol 11, 571–578 (2015). https://doi.org/10.1038/nchembio.1859

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