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Article

Lysines 207 and 325 methylation of WDR5 catalyzed by SETD6 promotes breast cancer cell proliferation and migration

  • Authors:
    • Ruosi Yao
    • Yingli Wang
    • Danyang Han
    • Yuhui Ma
    • Musong Ma
    • Yaping Zhao
    • Jiang Tan
    • Jun Lu
    • Guiying Xu
    • Xiaoxue Li
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024, P.R. China, Department of Toxicology, Jilin Province Institution of Tumor Research, Changchun, Jilin 130000, P.R. China, Department of Hematology, Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China, Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024, P.R. China, Department of Breast Surgery, Tumor Hospital of Jilin Province, Changchun, Jilin 130000, P.R. China
  • Pages: 3069-3077
    |
    Published online on: August 23, 2018
       https://doi.org/10.3892/or.2018.6669
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Abstract

Accumulating evidence has revealed that the methylation of lysines on nonhistones by histone lysine methyltransferases (HMTs) is crucial for regulating tumo­rigenesis and metastasis. However, whether the methy­lation of lysines on HMT complex components occurs and has functions in cancer progression is less well understood. WD repeat domain 5 (WDR5) is a core component of an HMT complex named mixed lineage leukemia (MLL)/Suppressor of Variegation, Enhancer of Zeste, and Trithorax 1 (SET1). In the present study, it was reported that lysines 207 and 325 (K207 and K325, respectively) of WDR5 were monomethylated by SET‑domain‑containing protein methyltransferase 6. Disrupting the methylation of K207/K325 via a K207R/K325R double‑site mutation attenuated the WDR5 promotion of breast cancer cell proliferation and migration. Methylation of K207/K325 on WDR5 partially contributed to maintaining global histone tri‑methylation of lysine 4 on histone H3 levels, but did not affect MLL/SET1 complex assembly. These results further understanding of a potential post‑translational modification of WDR5, and imply that the methylation of lysines on HMT complex components is crucial for regulating human carcinogenesis.
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1 

Dou Y, Milne TA, Ruthenburg AJ, Lee S, Lee JW, Verdine GL, Allis CD and Roeder RG: Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nat Struct Mol Biol. 13:713–719. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Han Z, Guo L, Wang H, Shen Y, Deng XW and Chai J: Structural basis for the specific recognition of methylated histone H3 lysine 4 by the WD-40 protein WDR5. Mol Cell. 22:137–144. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Ang YS, Tsai SY, Lee DF, Monk J, Su J, Ratnakumar K, Ding J, Ge Y, Darr H, Chang B, et al: Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network. Cell. 145:183–197. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Wysocka J, Swigut T, Milne TA, Dou Y, Zhang X, Burlingame AL, Roeder RG, Brivanlou AH and Allis CD: WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. Cell. 121:859–872. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Kim JY, Banerjee T, Vinckevicius A, Luo Q, Parker JB, Baker MR, Radhakrishnan I, Wei JJ, Barish GD and Chakravarti D: A role for WDR5 in integrating threonine 11 phosphorylation to lysine 4 methylation on histone H3 during androgen signaling and in prostate cancer. Mol Cell. 54:613–625. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Chen X, Gu P, Li K, Xie W, Chen C, Lin T and Huang J: Gene expression profiling of WDR5 regulated genes in bladder cancer. Genom Data. 5:27–29. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Tan X, Chen S, Wu J, Lin J, Pan C, Ying X, Pan Z, Qiu L, Liu R, Geng R, et al: PI3K/AKT-mediated upregulation of WDR5 promotes colorectal cancer metastasis by directly targeting ZNF407. Cell Death Dis. 8:e26862017. View Article : Google Scholar : PubMed/NCBI

8 

Ge Z, Song EJ, Kawasawa YI, Li J, Dovat S and Song C: WDR5 high expression and its effect on tumorigenesis in leukemia. Oncotarget. 7:37740–37754. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Chen X, Xie W, Gu P, Cai Q, Wang B, Xie Y, Dong W, He W, Zhong G, Lin T, et al: Upregulated WDR5 promotes proliferation, self-renewal and chemoresistance in bladder cancer via mediating H3K4 trimethylation. Sci Rep. 5:82932015. View Article : Google Scholar : PubMed/NCBI

10 

Clarke SG: Protein methylation at the surface and buried deep: Thinking outside the histone box. Trends Biochem Sci. 38:243–252. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Shi Y and Whetstine JR: Dynamic regulation of histone lysine methylation by demethylases. Mol Cell. 25:1–14. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Bedford MT and Clarke SG: Protein arginine methylation in mammals: Who, what, and why. Mol Cell. 33:1–13. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Chuikov S, Kurash JK, Wilson JR, Xiao B, Justin N, Ivanov GS, McKinney K, Tempst P, Prives C, Gamblin SJ, et al: Regulation of p53 activity through lysine methylation. Nature. 432:353–360. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Huang J, Perez-Burgos L, Placek BJ, Sengupta R, Richter M, Dorsey JA, Kubicek S, Opravil S, Jenuwein T and Berger SL: Repression of p53 activity by Smyd2-mediated methylation. Nature. 444:629–632. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Shi X, Kachirskaia I, Yamaguchi H, West LE, Wen H, Wang EW, Dutta S, Appella E and Gozani O: Modulation of p53 function by SET8-mediated methylation at lysine 382. Mol Cell. 27:636–646. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Vershinin Z, Feldman M, Chen A and Levy D: PAK4 methylation by SETD6 promotes the activation of the Wnt/β-catenin pathway. J Biol Chem. 291:6786–6795. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Bedford MT and Richard S: Arginine methylation an emerging regulator of protein function. Mol Cell. 18:263–272. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Wang L, Zhao Z, Meyer MB, Saha S, Yu M, Guo A, Wisinski KB, Huang W, Cai W, Pike JW, et al: CARM1 methylates chromatin remodeling factor BAF155 to enhance tumor progression and metastasis. Cancer Cell. 25:21–36. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Jansson M, Durant ST, Cho EC, Sheahan S, Edelmann M, Kessler B and La Thangue NB: Arginine methylation regulates the p53 response. Nat Cell Biol. 10:1431–1439. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Geng P, Zhang Y, Liu X, Zhang N, Liu Y, Liu X, Lin C, Yan X, Li Z, Wang G, et al: Automethylation of protein arginine methyltransferase 7 and its impact on breast cancer progression. FASEB J. 31:2287–2300. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Yao R, Jiang H, Ma Y, Wang L, Wang L, Du J, Hou P, Gao Y, Zhao L, Wang G, et al: PRMT7 induces epithelial-to-mesenchymal transition and promotes metastasis in breast cancer. Cancer Res. 74:5656–5667. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Zhao L, Zhang Y, Gao Y, Geng P, Lu Y, Liu X, Yao R, Hou P, Liu D, Lu J, et al: JMJD3 promotes SAHF formation in senescent WI38 cells by triggering an interplay between demethylation and phosphorylation of RB protein. Cell Death Differ. 22:1630–1640. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Zhao D and Huang Z: Effect of His-tag on expression, purification, and structure of zinc finger protein, ZNF191 (243–368). Bioinorg Chem Appl. 2016:82068542016. View Article : Google Scholar : PubMed/NCBI

24 

Hou P, Zhao Y, Li Z, Yao R, Ma M, Gao Y, Zhao L, Zhang Y, Huang B and Lu J: LincRNA-ROR induces epithelial-to-mesenchymal transition and contributes to breast cancer tumorigenesis and metastasis. Cell Death Dis. 5:e12872014. View Article : Google Scholar : PubMed/NCBI

25 

Levy D, Kuo AJ, Chang Y, Schaefer U, Kitson C, Cheung P, Espejo A, Zee BM, Liu CL, Tangsombatvisit S, et al: Lysine methylation of the NF-κB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-κB signaling. Nat Immunol. 12:29–36. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Trievel RC and Shilatifard A: WDR5, a complexed protein. Nat Struct Mol Biol. 16:678–680. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Binda O, Sevilla A, LeRoy G, Lemischka IR, Garcia BA and Richard S: SETD6 monomethylates H2AZ on lysine 7 and is required for the maintenance of embryonic stem cell self-renewal. Epigenetics. 8:177–183. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Mukherjee N, Cardenas E, Bedolla R and Ghosh R: SETD6 regulates NF-κB signaling in urothelial cell survival: Implications for bladder cancer. Oncotarget. 8:15114–15125. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Levy D, Liu CL, Yang Z, Newman AM, Alizadeh AA, Utz and Gozani O: A proteomic approach for the identification of novel lysine methyltransferase substrates. Epigenetics Chromatin. 4:192011. View Article : Google Scholar : PubMed/NCBI

30 

Song JJ and Kingston RE: WDR5 interacts with mixed lineage leukemia (MLL) protein via the histone H3-binding pocket. J Biol Chem. 283:35258–35264. 2008. View Article : Google Scholar : PubMed/NCBI

31 

Dharmarajan V, Lee JH, Patel A, Skalnik DG and Cosgrove MS: Structural basis for WDR5 interaction (Win) motif recognition in human SET1 family histone methyltransferases. J Biol Chem. 287:27275–27289. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Butler JS, Zurita-Lopez CI, Clarke SG, Bedford MT and Dent SY: Protein-arginine methyltransferase 1 (PRMT1) methylates Ash2L, a shared component of mammalian histone H3K4 methyltransferase complexes. J Biol Chem. 286:12234–12244. 2011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yao R, Wang Y, Han D, Ma Y, Ma M, Zhao Y, Tan J, Lu J, Xu G, Li X, Li X, et al: Lysines 207 and 325 methylation of WDR5 catalyzed by SETD6 promotes breast cancer cell proliferation and migration. Oncol Rep 40: 3069-3077, 2018.
APA
Yao, R., Wang, Y., Han, D., Ma, Y., Ma, M., Zhao, Y. ... Li, X. (2018). Lysines 207 and 325 methylation of WDR5 catalyzed by SETD6 promotes breast cancer cell proliferation and migration. Oncology Reports, 40, 3069-3077. https://doi.org/10.3892/or.2018.6669
MLA
Yao, R., Wang, Y., Han, D., Ma, Y., Ma, M., Zhao, Y., Tan, J., Lu, J., Xu, G., Li, X."Lysines 207 and 325 methylation of WDR5 catalyzed by SETD6 promotes breast cancer cell proliferation and migration". Oncology Reports 40.5 (2018): 3069-3077.
Chicago
Yao, R., Wang, Y., Han, D., Ma, Y., Ma, M., Zhao, Y., Tan, J., Lu, J., Xu, G., Li, X."Lysines 207 and 325 methylation of WDR5 catalyzed by SETD6 promotes breast cancer cell proliferation and migration". Oncology Reports 40, no. 5 (2018): 3069-3077. https://doi.org/10.3892/or.2018.6669
Copy and paste a formatted citation
x
Spandidos Publications style
Yao R, Wang Y, Han D, Ma Y, Ma M, Zhao Y, Tan J, Lu J, Xu G, Li X, Li X, et al: Lysines 207 and 325 methylation of WDR5 catalyzed by SETD6 promotes breast cancer cell proliferation and migration. Oncol Rep 40: 3069-3077, 2018.
APA
Yao, R., Wang, Y., Han, D., Ma, Y., Ma, M., Zhao, Y. ... Li, X. (2018). Lysines 207 and 325 methylation of WDR5 catalyzed by SETD6 promotes breast cancer cell proliferation and migration. Oncology Reports, 40, 3069-3077. https://doi.org/10.3892/or.2018.6669
MLA
Yao, R., Wang, Y., Han, D., Ma, Y., Ma, M., Zhao, Y., Tan, J., Lu, J., Xu, G., Li, X."Lysines 207 and 325 methylation of WDR5 catalyzed by SETD6 promotes breast cancer cell proliferation and migration". Oncology Reports 40.5 (2018): 3069-3077.
Chicago
Yao, R., Wang, Y., Han, D., Ma, Y., Ma, M., Zhao, Y., Tan, J., Lu, J., Xu, G., Li, X."Lysines 207 and 325 methylation of WDR5 catalyzed by SETD6 promotes breast cancer cell proliferation and migration". Oncology Reports 40, no. 5 (2018): 3069-3077. https://doi.org/10.3892/or.2018.6669
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