Interaction of YAP with the Myb-MuvB (MMB) complex defines a transcriptional program to promote the proliferation of cardiomyocytes
Autoři:
Marco Gründl aff001; Susanne Walz aff002; Laura Hauf aff001; Melissa Schwab aff001; Kerstin Marcela Werner aff001; Susanne Spahr aff001; Clemens Schulte aff003; Hans Michael Maric aff003; Carsten P. Ade aff001; Stefan Gaubatz aff001
Působiště autorů:
Theodor Boveri Institute and Comprehensive Cancer Center Mainfranken, Biocenter University of Wuerzburg, Wuerzburg, Germany
aff001; Comprehensive Cancer Center Mainfranken, Core Unit Bioinformatics, Biocenter, University of Wuerzburg, Wuerzburg, Germany
aff002; Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Wuerzburg, Germany
aff003
Vyšlo v časopise:
Interaction of YAP with the Myb-MuvB (MMB) complex defines a transcriptional program to promote the proliferation of cardiomyocytes. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008818
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008818
Souhrn
The Hippo signalling pathway and its central effector YAP regulate proliferation of cardiomyocytes and growth of the heart. Using genetic models in mice we show that the increased proliferation of embryonal and postnatal cardiomyocytes due to loss of the Hippo-signaling component SAV1 depends on the Myb-MuvB (MMB) complex. Similarly, proliferation of postnatal cardiomyocytes induced by constitutive active YAP requires MMB. Genome studies revealed that YAP and MMB regulate an overlapping set of cell cycle genes in cardiomyocytes. Protein-protein interaction studies in cell lines and with recombinant proteins showed that YAP binds directly to B-MYB, a subunit of MMB, in a manner dependent on the YAP WW domains and a PPXY motif in B-MYB. Disruption of the interaction by overexpression of the YAP binding domain of B-MYB strongly inhibits the proliferation of cardiomyocytes. Our results point to MMB as a critical downstream effector of YAP in the control of cardiomyocyte proliferation.
Klíčová slova:
Cardiac ventricles – Cardiomyocytes – Cell cycle and cell division – Gene expression – Heart – Immunoblotting – Immunoprecipitation – Mitosis
Zdroje
1. Hong W, Guan K-L. The YAP and TAZ transcription co-activators: key downstream effectors of the mammalian Hippo pathway. Seminars in cell & developmental biology. 2012;23: 785–793. doi: 10.1016/j.semcdb.2012.05.004 22659496
2. Meng Z, Moroishi T, Guan K-L. Mechanisms of Hippo pathway regulation. Genes Dev. 2016;30: 1–17. doi: 10.1101/gad.274027.115 26728553
3. Liu S, Martin JF. The regulation and function of the Hippo pathway in heart regeneration. Wiley Interdiscip Rev Dev Biol. John Wiley & Sons, Ltd (10.1111); 2019;8: e335. doi: 10.1002/wdev.335 30169913
4. Wang J, Liu S, Heallen T, Martin JF. The Hippo pathway in the heart: pivotal roles in development, disease, and regeneration. Nat Rev Cardiol. Nature Publishing Group; 2018;15: 672–684. doi: 10.1038/s41569-018-0063-3 30111784
5. Gise von A, Lin Z, Schlegelmilch K, Honor LB, Pan GM, Buck JN, et al. YAP1, the nuclear target of Hippo signaling, stimulates heart growth through cardiomyocyte proliferation but not hypertrophy. Proc Natl Acad Sci USA. 2012;109: 2394–2399. doi: 10.1073/pnas.1116136109 22308401
6. Monroe TO, Hill MC, Morikawa Y, Leach JP, Heallen T, Cao S, et al. YAP Partially Reprograms Chromatin Accessibility to Directly Induce Adult Cardiogenesis In Vivo. Dev Cell. 2019;48: 765–779.e7. doi: 10.1016/j.devcel.2019.01.017 30773489
7. Heallen T, Zhang M, Wang J, Bonilla-Claudio M, Klysik E, Johnson RL, et al. Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size. Science. 2011;332: 458–461. doi: 10.1126/science.1199010 21512031
8. Heallen T, Morikawa Y, Leach J, Tao G, Willerson JT, Johnson RL, et al. Hippo signaling impedes adult heart regeneration. Development. 2013;140: 4683–4690. doi: 10.1242/dev.102798 24255096
9. Xin M, Kim Y, Sutherland LB, Qi X, McAnally J, Schwartz RJ, et al. Regulation of insulin-like growth factor signaling by Yap governs cardiomyocyte proliferation and embryonic heart size. Science signaling. 2011;4: ra70. doi: 10.1126/scisignal.2002278 22028467
10. Morikawa Y, Zhang M, Heallen T, Leach J, Tao G, Xiao Y, et al. Actin cytoskeletal remodeling with protrusion formation is essential for heart regeneration in Hippo-deficient mice. Science signaling. American Association for the Advancement of Science; 2015;8: ra41–ra41. doi: 10.1126/scisignal.2005781 25943351
11. Leach JP, Heallen T, Zhang M, Rahmani M, Morikawa Y, Hill MC, et al. Hippo pathway deficiency reverses systolic heart failure after infarction. Nature. 2017;550: 260–264. doi: 10.1038/nature24045 28976966
12. Lin Z, Gise von A, Zhou P, Gu F, Ma Q, Jiang J, et al. Cardiac-specific YAP activation improves cardiac function and survival in an experimental murine MI model. Circ Res. 2014;115: 354–363. doi: 10.1161/CIRCRESAHA.115.303632 24833660
13. Totaro A, Panciera T, Piccolo S. YAP/TAZ upstream signals and downstream responses. Nat Cell Biol. Nature Publishing Group; 2018;20: 888–899. doi: 10.1038/s41556-018-0142-z 30050119
14. Pattschull G, Walz S, Gründl M, Schwab M, Rühl E, Baluapuri A, et al. The Myb-MuvB Complex Is Required for YAP-Dependent Transcription of Mitotic Genes. Cell Rep. 2019;27: 3533–3546.e7. doi: 10.1016/j.celrep.2019.05.071 31216474
15. Sadasivam S, DeCaprio JA. The DREAM complex: master coordinator of cell cycle-dependent gene expression. Nat Rev Cancer. 2013;13: 585–595. doi: 10.1038/nrc3556 23842645
16. Fischer M, Müller GA. Cell cycle transcription control: DREAM/MuvB and RB-E2F complexes. Crit Rev Biochem Mol Biol. 2017;: 1–25. doi: 10.1080/10409238.2017.1360836 28799433
17. Guiley KZ, Liban TJ, Felthousen JG, Ramanan P, Litovchick L, Rubin SM. Structural mechanisms of DREAM complex assembly and regulation. Genes Dev. 2015;29: 961–974. doi: 10.1101/gad.257568.114 25917549
18. Litovchick L, Sadasivam S, Florens L, Zhu X, Swanson SK, Velmurugan S, et al. Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence. Mol Cell. 2007;26: 539–551. doi: 10.1016/j.molcel.2007.04.015 17531812
19. Schmit F, Korenjak M, Mannefeld M, Schmitt K, Franke C, Eyss von B, et al. LINC, a human complex that is related to pRB-containing complexes in invertebrates regulates the expression of G2/M genes. Cell Cycle. 2007;6: 1903–1913. doi: 10.4161/cc.6.15.4512 17671431
20. Osterloh L, Eyss von B, Schmit F, Rein L, Hübner D, Samans B, et al. The human synMuv-like protein LIN-9 is required for transcription of G2/M genes and for entry into mitosis. EMBO J. 2007;26: 144–157. doi: 10.1038/sj.emboj.7601478 17159899
21. Pilkinton M, Sandoval R, Colamonici OR. Mammalian Mip/LIN-9 interacts with either the p107, p130/E2F4 repressor complex or B-Myb in a cell cycle-phase-dependent context distinct from the Drosophila dREAM complex. Oncogene. 2007;26: 7535–7543. doi: 10.1038/sj.onc.1210562 17563750
22. Sadasivam S, Duan S, DeCaprio JA. The MuvB complex sequentially recruits B-Myb and FoxM1 to promote mitotic gene expression. Genes Dev. 2012;26: 474–489. doi: 10.1101/gad.181933.111 22391450
23. Cai J, Zhang N, Zheng Y, de Wilde RF, Maitra A, Pan D. The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program. Genes Dev. Cold Spring Harbor Lab; 2010;24: 2383–2388. doi: 10.1101/gad.1978810 21041407
24. Zanconato F, Forcato M, Battilana G, Azzolin L, Quaranta E, Bodega B, et al. Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. Nat Cell Biol. Nature Publishing Group; 2015;17: 1218–1227. doi: 10.1038/ncb3216 26258633
25. Stein C, Bardet AF, Roma G, Bergling S, Clay I, Ruchti A, et al. YAP1 Exerts Its Transcriptional Control via TEAD-Mediated Activation of Enhancers. PLoS Genet. 2015;11: e1005465. doi: 10.1371/journal.pgen.1005465 26295846
26. Galli GG, Carrara M, Yuan W-C, Valdes-Quezada C, Gurung B, Pepe-Mooney B, et al. YAP Drives Growth by Controlling Transcriptional Pause Release from Dynamic Enhancers. Mol Cell. 2015;60: 328–337. doi: 10.1016/j.molcel.2015.09.001 26439301
27. Agah R, Frenkel PA, French BA, Michael LH, Overbeek PA, Schneider MD. Gene recombination in postmitotic cells. Targeted expression of Cre recombinase provokes cardiac-restricted, site-specific rearrangement in adult ventricular muscle in vivo. J Clin Invest. 1997;100: 169–179. doi: 10.1172/JCI119509 9202069
28. Muzumdar MD, Tasic B, Miyamichi K, Li L, Luo L. A global double-fluorescent Cre reporter mouse. Genesis. John Wiley & Sons, Ltd; 2007;45: 593–605. doi: 10.1002/dvg.20335 17868096
29. Guiley KZ, Iness AN, Saini S, Tripathi S, Lipsick JS, Litovchick L, et al. Structural mechanism of Myb-MuvB assembly. Proc Natl Acad Sci USA. National Academy of Sciences; 2018;115: 10016–10021. doi: 10.1073/pnas.1808136115 30224471
30. Macias MJ, Martin-Malpartida P, Massagué J. Structural determinants of Smad function in TGF-β signaling. Trends Biochem Sci. 2015;40: 296–308. doi: 10.1016/j.tibs.2015.03.012 25935112
31. Chen HI, Sudol M. The WW domain of Yes-associated protein binds a proline-rich ligand that differs from the consensus established for Src homology 3-binding modules. Proc Natl Acad Sci USA. National Academy of Sciences; 1995;92: 7819–7823. doi: 10.1073/pnas.92.17.7819 7644498
32. Werwein E, Schmedt T, Hoffmann H, Usadel C, Obermann N, Singer JD, et al. B-Myb promotes S-phase independently of its sequence-specific DNA binding activity and interacts with polymerase delta-interacting protein 1 (Pdip1). Cell Cycle. Taylor & Francis; 2012;11: 4047–4058. doi: 10.4161/cc.22386 23032261
33. Xin M, Kim Y, Sutherland LB, Murakami M, Qi X, McAnally J, et al. Hippo pathway effector Yap promotes cardiac regeneration. Proc Natl Acad Sci USA. 2013;110: 13839–13844. doi: 10.1073/pnas.1313192110 23918388
34. Del Re DP, Yang Y, Nakano N, Cho J, Zhai P, Yamamoto T, et al. Yes-associated protein isoform 1 (Yap1) promotes cardiomyocyte survival and growth to protect against myocardial ischemic injury. J Biol Chem. 2013;288: 3977–3988. doi: 10.1074/jbc.M112.436311 23275380
35. Quaife-Ryan GA, Sim CB, Ziemann M, Kaspi A, Rafehi H, Ramialison M, et al. Multicellular Transcriptional Analysis of Mammalian Heart Regeneration. Circulation. 2017;136: 1123–1139. doi: 10.1161/CIRCULATIONAHA.117.028252 28733351
36. Zhao B, Kim J, Ye X, Lai Z-C, Guan K-L. Both TEAD-binding and WW domains are required for the growth stimulation and oncogenic transformation activity of yes-associated protein. Cancer Res. American Association for Cancer Research; 2009;69: 1089–1098. doi: 10.1158/0008-5472.CAN-08-2997 19141641
37. Reichert N, Wurster S, Ulrich T, Schmitt K, Hauser S, Probst L, et al. Lin9, a subunit of the mammalian DREAM complex, is essential for embryonic development, for survival of adult mice, and for tumor suppression. Mol Cell Biol. 2010;30: 2896–2908. doi: 10.1128/MCB.00028-10 20404087
38. Stanley EG, Biben C, Elefanty A, Barnett L, Koentgen F, Robb L, et al. Efficient Cre-mediated deletion in cardiac progenitor cells conferred by a 3'UTR-ires-Cre allele of the homeobox gene Nkx2-5. Int J Dev Biol. 2002;46: 431–439. 12141429
39. Hameyer D, Loonstra A, Eshkind L, Schmitt S, Antunes C, Groen A, et al. Toxicity of ligand-dependent Cre recombinases and generation of a conditional Cre deleter mouse allowing mosaic recombination in peripheral tissues. Physiol Genomics. 2007;31: 32–41. doi: 10.1152/physiolgenomics.00019.2007 17456738
40. Komuro A, Nagai M, Navin NE, Sudol M. WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus. J Biol Chem. 2003;278: 33334–33341. doi: 10.1074/jbc.M305597200 12807903
41. Oka T, Mazack V, Sudol M. Mst2 and Lats kinases regulate apoptotic function of Yes kinase-associated protein (YAP). J Biol Chem. American Society for Biochemistry and Molecular Biology; 2008;283: 27534–27546. doi: 10.1074/jbc.M804380200 18640976
42. Tavner F, Frampton J, Watson RJ. Targeting an E2F site in the mouse genome prevents promoter silencing in quiescent and post-mitotic cells. Oncogene. 2007;26: 2727–2735. doi: 10.1038/sj.onc.1210087 17072340
43. He A, Ma Q, Cao J, Gise von A, Zhou P, Xie H, et al. Polycomb repressive complex 2 regulates normal development of the mouse heart. Circ Res. 2012;110: 406–415. doi: 10.1161/CIRCRESAHA.111.252205 22158708
44. Azzolin L, Panciera T, Soligo S, Enzo E, Bicciato S, Dupont S, et al. YAP/TAZ incorporation in the β-catenin destruction complex orchestrates the Wnt response. Cell. 2014;158: 157–170. doi: 10.1016/j.cell.2014.06.013 24976009
45. Knight AS, Notaridou M, Watson RJ. A Lin-9 complex is recruited by B-Myb to activate transcription of G2/M genes in undifferentiated embryonal carcinoma cells. Oncogene. 2009;28: 1737–1747. doi: 10.1038/onc.2009.22 19252525
46. Frank R. Spot-synthesis: an easy technique for the positionally addressable, parallel chemical synthesis on a membrane support. Tetrahedron. Pergamon; 1992;48: 9217–9232. doi: 10.1016/S0040-4020(01)85612-X
47. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. BioMed Central; 2013;14: R36. doi: 10.1186/gb-2013-14-4-r36 23618408
48. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. Nature Publishing Group; 2012;9: 357–359. doi: 10.1038/nmeth.1923 22388286
49. Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. BioMed Central; 2008;9: R137. doi: 10.1186/gb-2008-9-9-r137 18798982
50. Quinlan AR, Hall IM. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010;26: 841–842. doi: 10.1093/bioinformatics/btq033 20110278
51. Ramírez F, Dündar F, Diehl S, Grüning BA, Manke T. deepTools: a flexible platform for exploring deep-sequencing data. Nucleic Acids Res. 2014;42: W187–91. doi: 10.1093/nar/gku365 24799436
52. Sloan CA, Chan ET, Davidson JM, Malladi VS, Strattan JS, Hitz BC, et al. ENCODE data at the ENCODE portal. Nucleic Acids Res. 2016;44: D726–32. doi: 10.1093/nar/gkv1160 26527727
53. Edgar R, Domrachev M, Lash AE. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2002;30: 207–210. doi: 10.1093/nar/30.1.207 11752295
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