Motoki Takaku

Our laboratory is interested in understanding the function of chromatin regulators (transcription factors and chromatin remodelers) in cancer. Recent large-scale genome profiling revealed frequent mutations on chromatin regulator genes in various cancers. By using a combination of genomics, biochemistry, and genome editing techniques, we study basic mechanisms and cancer specific functions of chromatin regulators. 

1. Saotome M, Poduval DB, Nair R, Cooper M, Takaku M. GATA3 truncation mutants alter EMT related gene expression via partial motif recognition in luminal breast cancer cells. (2022) Frontiers in Genetics. doi: 10.1038/s41467-018-03478-4
2. Ansari KI, Bhan A, Saotome M, Tyagi A, De Kumar B, Chen C, Takaku M, Jandial R. Autocrine GM-CSF signaling contributes to growth of HER2+ breast leptomeningeal carcinomatosis. (2021) Cancer Res. doi: 10.1158/0008-5472.CAN-21-0259.
3. Saotome M, Takaku M. Analysis of protein complexes using gel filtration chromatography. (2021) Protein Archives
4. Tanaka H*, Takizawa Y*, Takaku M*, Kato D, Kumagawa Y, Grimm SA, Wade PA, Kurumizaka K. (*first authors) Interaction of the pioneer transcription factor GATA3 with nucleosomes. (2020) Nat Commun 11(1):4136. doi: 10.1038/s41467-020-17959-y
5. Takaku M*, Grimm SA, Kumar BD, Bennett BD, and Wade PA* (*corresponding authors) Cancer-specific mutation of GATA3 disrupts the transcriptional regulatory network governed by Estrogen Receptor alpha, FOXA1 and GATA3. (2020) Nucleic Acids Res
6. Machida S, Depierre D, Chen HC, Thenin-Houssier S, Petitjean G, Doyen C, Takaku M, Cuvier O and Benkirane M. Exploring histone loading on unintegrated HIV DNA reveals a dynamic nucleosome positioning between unintegrated and integrated viral genome. (2020) Proc Natl Acad Sci U S A
7. Weiss K, Lazar HP, Kurolap A, Martinez AF, Paperna T, Cohen L, Smeland MF, Wallen S, Solveig H, Keren B, Terhal P, Irving M, Takaku M,…, Lachlan K. (2019) The CHD4-related syndrome: a comprehensive investigation of the clinical spectrum, genotype-phenotype correlations, and molecular basis. Genet Med, doi: 10.1038/s41436-019-0612-0
8. Grimm SA, Shimbo T, Takaku M, Thomas JW, Auerbach S, Bennett B, Bucher JR, Burkholder AB, Day F, Du Y, French JE, Li J, Merrick BA. Tice RR, Wang T, Xu X, Bushel P, Fargo DC, Mullikin JC, Wade PA. DNA methylation in mice is influenced by genetics as well as sex and life experience, Nat Commun, 10(1)
9. Blok LS, Rousseau J, Twist J, Ehresmann S, Takaku M, et al. (2018) Missense mutations disrupting the helicase domain of chromatin remodeller CHD3 cause a novel neurodevelopmental syndrome with intellectual disability, macrocephaly and impaired speech and language, Nat Commun, 9 (4619)
10. Takaku M, Grimm SA, Roberts JD, Chrysovergis K, Bennett BD, Myers P, Perera L, Tucker CJ, Perou CM, and Wade PA. (2018) GATA3 Zinc Finger 2 mutations reprogram the breast cancer transcriptional network, Nat Commun, 9 (1) 
11. Li P, Wang L, Bennett BD, Wang J, Li J, Qin Y, Takaku M, Wade PA, Wong J, Hu G (2017) Rif1 Promotes a Repressive Chromatin State to Safeguard Against Endogenous Retrovirus Activation, Nucleic Acids Res, 45(22):12723-12738
12. Zhang S, Takaku M, Zou L, Gu A, Chou W, Zhang G, Wu B, Kong Q, Thomas SY, Serody JS, Chen X, Xu X, Wade PA, Cook DN, Ting JP, Wan YY (2017) Releasing Ski-Smad4 mediated suppression is essential to license Th17 differentiation, Nature, 551(7678):105-109
13. Thomas SY, Whitehead GS, Takaku M, Ward JM, Xu X, Nakano K, Lyons-Cohen MR, Nakano H, Gowdy KM, Wade PA, Cook DN (2017) MyD88-dependent Dendritic and Epithelial Cell Crosstalk Orchestrates Immune Responses to Allergens, Mucosal Immunol, doi: 10.1038/mi.2017.84
14. Kobayashi W, Takaku M, Machida S, Tachiwana H, Maehara K, Ohkawa Y, Kurumizaka H (2016) Chromatin architecture may dictate the target site for DMC1, but not for RAD51, during homologous pairing, Sci Rep, 6:24228
15. Shimbo T, Takaku M, Wade PA (2016) High-quality ChIP-seq analysis of MBD3 in human breast cancer cells, Genom Data, 7:173-4
16. Takaku M, Grimm SA, Shimbo T, Perera L, Menafra R, Stunnenberg HG, Archer TK, Machida S, Kurumizaka H, Wade PA (2016) GATA3-dependent cellular reprogramming requires activation-domain dependent recruitment of a chromatin remodeler, Genome Biol, 17(1):36
17. Machida M, Hayashida R, Takaku M, Fukuto A, Sun J, Kinomura A, Tashiro S, Kurumizaka H (2016) Relaxed Chromatin Formation and Weak Suppression of Homologous Pairing by the Testis-Specific Linker Histone H1T, Biochemistry, 55(4):637-46
18. Takaku M, Grimm SA, Wade PA. (2015) GATA3 in Breast Cancer: Tumor Suppressor or Oncogene?, Gene Expr, 16(4)
19. Machida S*, Takaku M*, Ikura M, Sun J, Suzuki H, Kobayashi W, Kinomura A, Osakabe A, Tachiwana H, Horikoshi Y, Fukuto A, Matsuda R, Ura K, Tashiro S, Ikura T, Kurumizaka H. (2014) *co-first authors. Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1, Sci Rep, 4:4863
20. Adomas AB, Grimm SA, Malone C, Takaku M, Sims JK, Wade PA. (2014) Breast tumor specific mutation in GATA3 affects physiological mechanisms regulating transcription factor turnover, BMC Cancer, 14:278
21. Osakabe A, Tachiwana H, Takaku M, Hori T, Obuse C, Kimura H, Fukagawa T, Kurumizaka H. (2013) Vertebrate Spt2 is a novel nucleolar histone chaperone that assists in ribosomal DNA transcription, J Cell Sci, 126(Pt 6):1323-1332
22. Morozumi Y, Ino R, Takaku M, Hosokawa M, Chuma S, Kurumizaka H. (2012) Human PSF concentrates DNA and stimulates duplex capture in DMC1-mediated homologous pairing, Nucleic Acids Res, 40(7):3031-3041
23. Takaku M*, Tsujita T*, Horikoshi N, Takizawa Y, Qing Y, Hirota K, Ikura M, Ikura T, Takeda S, Kurumizaka H. (2011) *co-first authors. Purification of the human SMN-GEMIN2 complex and assessment of its stimulation of RAD51-mediated DNA recombination reactions, Biochemistry, 50(32):6797-6805
24. Takaku M*, Ueno H*, and Kurumizaka H. (2011) *co-first authors. Biochemical analysis of the human Ena/Vasp-family proteins, MENA, VASP, and EVL, in homologous recombination., J Biochem, 149(6):721-729
25. Takaku M*, Kainuma T*, Ishida-Takaku T, Ishigami S, Suzuki H, Tashiro S, van Soest RW, Nakao Y and Kurumizaka H. (2011) *co-first authors. Halenaquinone, a chemical compound that specifically inhibits the secondary DNA binding of RAD51., Genes Cell., 16(4):427-436
26. Takaku M, Takahashi D, Machida S, Ueno H, Hosoya N, Ikawa S, Miyagawa K, Shibata T, Kurumizaka H. (2010) Single-stranded DNA catenation mediated by human EVL and a type I topoisomerase, Nucleic Acids Res, 38(21):7579-7586.
27. Takizawa Y, Qing Y, Takaku M, Ishida T, Morozumi Y, Tsujita T, Kogame T, Hirota K, Takahashi M, Shibata T, Kurumizaka H, Takeda S. (2010) GEMIN2 promotes accumulation of RAD51 at double-strand breaks in homologous recombination, Nucleic Acids Res, 38(15):5059-5074
28. Horikoshi N, Morozumi Y, Takaku M, Takizawa Y, Kurumizaka H. (2010) Holliday junction-binding activity of human SPF45., Genes Cell., 15(4):373-383
29. Takaku M, Machida S, Nakayama S, Takahashi D, Kurumizaka H. (2009) Biochemical analysis of the human EVL domains in homologous recombination, FEBS J, 276(20):5841-5848
30. Morozumi Y, Takizawa Y, Takaku M, Kurumizaka H. (2009) Human PSF binds to RAD51 and modulates its homologous-pairing and strand-exchange activities, Nucleic Acids Res, 37(13):4296-4307.
31. Katsura M, Tsuruga T, Date O, Yoshihara T, Ishida M, Tomoda Y, Okajima M, Takaku M, Kurumizaka H, Kinomura A, Mishima HK, Miyagawa K. (2009) The ATR-Chk1 pathway plays a role in the generation of centrosome aberrations induced by Rad51C dysfunction, Nucleic Acids Res, 37(12):3959-3968
32. Takaku M, Machida S, Hosoya N, Nakayama S, Takizawa Y, Sakane I, Shibata T, Miyagawa K, Kurumizaka H. (2009) Recombination activator function of the novel RAD51- and RAD51B-binding protein, human EVL, J Biol Chem, 284(21):14326-14336

Postdoc training, Dr. Paul A. Wade laboratory, ESCBL, National Institutes of Environmental Health Sciences, RTP, NC.

Ph.D., Waseda University, Tokyo, Japan

M.Sc., Waseda University, Tokyo, Japan

B.Sc., Waseda University, Tokyo, Japan