Kyoko Yokomori

Professor, Biological Chemistry
School of Medicine

PH.D., University of Southern California

D.V.M./Ph.D., University of Tokyo, Faculty of Agriculture, Dept.

Phone: (949) 824-8215, 2158
Fax: (949) 824-2688

University of California, Irvine
H129, Hitachi Plumwood
Mail Code: 1700
Irvine, CA 92697

picture of Kyoko  Yokomori

Epigenetics, epigenomics, FSHD, CdLS, cohesin, condensin, SMC complex, DNA damage response and repair, gene regulation, higher-order chromatin organization, chromosome dynamics
1990-1991 Fieger Pre-doctoral Fellowship
1993-1996 Leukemia Society of America Fellow
1996-1999 Leukemia Society of America Special Fellow
1999-2001 March of Dimes Basil O’Connor Starter Scholar Research Award
2000-2005 Leukemia & Lymphoma Society Scholar
Appointments 1991 – 1992 Postdoctoral Fellow, Dr. Michael Lai's laboratory, Howard Hughes Medical Institute,
University of Southern California, Department of Microbiology
1992 – 1997 Postdoctoral Fellow, Dr. Robert Tjian's laboratory, Howard Hughes Medical Institute,
University of California, Berkeley
Chromosomes are essential components of the cell, storing genetic information necessary to carry out the normal life cycle of the cell. They serve as templates for replication and transcription, and undergo mitosis to maintain genetic information over generations. To achieve these multiple roles, chromosomes exhibit dynamic structural changes in a cell cycle-dependent manner. Although genetic studies identified various important cell cycle regulators such as cyclin and cdks, the actual molecular machine that drives structural changes of chromosomes in response to these cell cycle regulators remains elusive. In recent years, the SMC (structural maintenance of chromosomes) family proteins were found to play important roles in several fundamental chromosome functions including chromosome condensation, segregation, recombination, repair and X chromosome dosage compensation. The SMC proteins are physically associated with chromosomes, suggesting that they may be part of the machinery that regulates local and global structural changes of chromosomes required for these functions. The research objective of our laboratory is to biochemically identify and characterize the SMC-containing multiprotein complexes in human cells that modulate higher order chromatin structure, and study how their function is regulated during cell cycle using biochemical, cell biological and genetic approaches.
Publications Selected publications
(Univ. Tokyo)
1. Yokomori, K., Okada, N., Murai, Y., Goto, N., and Fujiwara, K. (1989). Enterohepatitis in Mongolian gerbils (Meriones unguiculatus) inoculated perorally with Tyzzer's organism (Bacillus piliformis). Laboratory Animal Science 39: 16-20.

(Univ. Southern California)
3. Yokomori, K., La Monica, N., Makino, S., Shieh, C.-K., and Lai, M.M.C. (1989). Biosynthesis, structure and biological activities of envelope protein gp65 of murine coronavirus. Virology 173 : 683-691.

8. Yokomori, K., Baker, S.C., Stohlman, S.A., and Lai, M.M.C. (1992). Hemagglutinin-esterase-specific monoclonal antibodies alter the neuropathogenicity of mouse hepatitis virus. J. Virol. 66 : 2865-2874.

9. Yokomori, K., Banner, L.R., and Lai, M.M.C. (1992). Coronavirus mRNA transcription: UV light transcriptional mapping studies suggest an early requirement for a genomic-length template. J. Virol. 66: 4671-4678.

10. Yokomori, K. and Lai, M. M. C. (1992). Mouse hepatitis virus utilizes two carcinoembryonic antigens as alternative receptors. J. Virol. 66: 6194-6199.

11. Yokomori, K. and Lai, M. M. C. (1992). The receptor for mouse hepatitis virus in the resistant mouse strain SJL is functional: implications for the requirement of a second factor for viral infection. J. Virol. 66: 6931-6938.

17. Chen, D.S., Asanaka, M., Yokomori, K., Wang, F.-I., Hwang, S. B., Li, H.-P., and Lai, M.M.C. (1995). A novel pregnancy-specific glycoprotein is expressed in the brain and serves as a receptor for mouse hepatitis virus. Proc. Natl. Acad. Sci. USA 92: 12095-12099.

(UC Berkeley)
19. Yokomori, K., Admon, A., Goodrich, J.A., Chen, J.-L., and Tjian, R. (1993). Drosophila TFIIA-L is processed into two subunits that are associated with the TBP/TAF complex. Genes & Dev. 7: 2235-2245.

20. Yokomori, K., Chen, J.-L., Admon, A., Zhou, S., and Tjian R. (1993). Molecular cloning and characterization of dTAFII30a and dTAFII30ß: two small subunits of Drosophila TFIID. Genes & Dev. 7: 2587-2597.

21. Verrijzer, C.P., Yokomori, K., Chen, J.-L., and Tjian, R. (1994). Drosophila TAFII150: similarity to yeast gene TSM-1 and specific binding to core promoter DNA. Science 264: 933-941.

22. Yokomori, K., Zeidler, M. P., Chen, J.-L., Verrijzer, C. P., Mlodzik, M., and Tjian, R. (1994). Drosophila TFIIA directs cooperative DNA binding with TBP and mediates transcriptional activation. Genes & Dev. 8: 2313-2323.

23. Chen, J.-L., Attardi, L. D., Verrijzer, C. P., Yokomori, K., and Tjian, R. (1994). Assembly of recombinant TFIID reveals differential coactivator requirements for distinct transcriptional activators. Cell 79: 93-105.

24. Verrijzer, C. P., Chen, J.-L., Yokomori, K., and Tjian, R. (1995). Binding of TAFs to core elements directs promoter selectivity by RNA polymerase II. Cell 81: 1115-1125.

25. Zeidler, M. P., Yokomori, K., Tjian, R., and Mlodzik, M. (1996). Drosophila TFIIA-S is up-regulated and required during Ras-mediated photoreceptor determination. Genes & Dev. 10: 50-59.

26. Yokomori, K., Verrijzer, C.P., and Tjian, R. (1998) An interplay between TBP, TFIIE and TFIIA modulates DNA binding and transcription. Proc. Natl. Acad. Sci. USA 95:6722-27

(UC Irvine)
27. Schmiesing, J.A., Ball, A.R., Gregson, H.C., Alderton, J., Zhou, S. and Yokomori, K. (1998) Identification of two distinct human SMC complexes involved in mitotic chromosome dynamics. Proc. Natl. Acad. Sci. USA 95:12906-11. PMC23650

28. Schmiesing, J. A., Gregson, H. C., Zhou, S., and Yokomori, K. (2000). A human condensin complex containing hCAP-C-hCAP-E and CNAP1, a homolog of Xenopus XCAP-D2, colocalizes with phosphorylated histone H3 during the early stage of mitotic chromosome condensation. Mol. Cell. Biol. 20: 6996-7006.

31. Gregson, H. C., Schmiesing, J. A., Kim, J.-S., Kobayashi, T., Zhou, S., and Yokomori, K. (2001). A potential role for human cohesin in mitotic spindle aster assembly. J. Biol. Chem. 276:47676-47682.

33. Ball, Jr. A. R., Zhou, C., Schmiesing, J. A. Gregson, H. C., Okada, Y., Doi, T., and Yokomori, K. (2002). Identification of a chromosome-targeting domain in the human condensin subunit CNAP1/hCAP-D2/Eg7. Mol. Cell. Biol. 22:5769-5781. PMC133980

34. Hakimi, M.-A., Bochar, D. A., Schmiesing, J. A., Dong, Y., Barak, O. G., Speicher, D. A., Yokomori, K., and Shiekhattar, R. (2002). A chromatin remodelling complex that loads cohesin onto human chromosomes. Nature 418:994-998.

36. Kim, J.-S., Krasieva, T. B., LaMorte, V., Taylor, A. M. R., and Yokomori, K. (2002). Specific recruitment of human cohesin to laser-induced DNA damage. J. Biol. Chem. 277:45149-45153.

38. Bermudez, V. P., Maniwa, Y., Tappin, I., Ozato, K., Yokomori, K., and Hurwitz, J. (2003). The alternative Ctf18-Dcc1-Ctf8-replication factor C complex required for sister chromatid cohesion loads proliferating cell nuclear antigen onto DNA. Proc. Natl. Acad. Sci. 100:10237–10242.

40. Kim, J.-S., Krasieva, T. B., Kurumizaka, H., Chen, D. J., Taylor, A. M. R., and Yokomori, K. (2005). Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells. J. Cell Biol. 170: 341-7. PMC2171485

41. Heale, J. A., Ball, Jr., A. R., Schmiesing, J. A., Kim, J.-S., Kong, X., Zhou, S., Hudson, D. F., Eanrshaw, W.C., and Yokomori, K. (2006). Condensin I interacts with the PARP-1-XRCC1 complex and functions in DNA single-strand break repair. Molecular Cell 21: 837-48.

44. Hou, F., Chu C. W., Kong, X., Yokomori, K., Zou, H. (2007). The acetyltransferase activity of San stabilizes the mitotic cohesin at the centromeres in a shugoshin-independent manner. J Cell Biol. 177: 587-97.

50. Parelho, V., Hadjur, S.,m Spivakov, M., Leleu, M., Sauer, S., Gregson, H. C., Jarmuz, A., Canzonetta, C., Webster, Z., Nesterova, T., Cobb, B. S., Yokomori, K., Dillon, N., Aragon, L., Fisher, A. G., Merkenschlager, M. (2008). Cohesins functionally associate with CTCF on mammalian chromosome arms. Cell 132: 422-33.

51. Kong, X., Ball, Jr., A. R., Sonoda, E., Feng, J., Takeda, S., Fukagawa, T., Yen, T. J., and Yokomori, K. (2009). Cohesin associates with spindle poles in a mitosis-specific manner and functions in spindle assembly in vertebrate cells. Mol. Biol. Cell 20: 1289-301. PMC2649254.

52. Kong, X., Mohanty, S., Stephens, J., Heale, J. T., Gomez-Godinez, V., Shi, L., Kim, J.-S., Yokomori, K.* and Berns, M. W.* (2009). Comparative analysis of different laser systems to study cellular responses to DNA damage in mammalian cells. Nucleic Acid Res. 37: e68. (* equal corresponding authors). PMC2685111.

53. Ball, Jr., A. R. and Yokomori, K. (2009). Revisiting the role of Heterochromatin Protein 1 in DNA repair. J. Cell Biol. 185: 573-5.

54. Zeng, W., de Greef, J. C., Chen, Y.-Y., Chien, R., Kong, X., Gregson, H. C., Winokur, S. T., Pyle, A., Robertson, K. D., Schmiesing, J. A., Kimonis, V. E., Balog, J., Frants. R. R., Ball, Jr., A. R., Lock, L. F., Donovan, P. J., van der Maarel, S., and Yokomori, K. (2009). Specific loss of histone H3 lysine 9 trimethylation and HP1?/cohesin binding at D4Z4 repeats is associated with facioscapulohumeral dystrophy (FSHD). PLoS Genet. 5: e1000559. PMC2700282.

56. Kawauchi, S., Calof, A. L., Santos, R., Lopez-Burks, M. E., Young, C. M., Hoang, M. P., Chua, A., Lao, T., Lechner, M. S., Daniel, J. A., Nussenzweig, A., Kitzes, L., Yokomori, K., Hallgrimsson, B., Lander, A. D. (2009). Multiple Organ System Defects and Transcriptional Dysregulation in the Nipbl+/- Mouse, a Model of Cornelia de Lange Syndrome. PLoS Genet. 5: e1000650. PMC2730539.

57. Yusufzai, T., Kong, X., Yokomori, K., and Kadonaga, J. T. (2009). The annealing helicase HARP is recruited to DNA repair sites via an interaction with RPA. Genes Dev. 23: 2000-4. PMC2764493.

58. Zeng, W., Ball, Jr., A. R., and Yokomori, K. (2010). HP1: heterochromatin binding proteins working the genome. Epigenetics 5: 287-92.

60. Wu, S., Wang, W., Kong, X., Congdon1, L. M., Yokomori, K., Kirschner, M. W., and Rice, J. C. (2010). Dynamic regulation of the PR-Set7 histone methyltransferase is required for normal cell cycle progression. Genes Dev. 24: 2531-42. PMC2975929.

61. Chien, R., Zeng, W., Kawauchi, S., Bender, M. A., Santos, R., Gregson, H. C., Schmiesing, J. A., Newkirk, D. A., Kong, X., Ball, Jr., A. R., Calof, A. L., Lander, A. D., Groudine. M., and Yokomori, K. (2011). Cohesin mediates chromatin interactions that regulate mammalian ß-globin expression. J. Biol. Chem. 286: 17870-8. PMC3093862.

62. Ball, Jr., A. R. and Yokomori, K. (2011). Chromatin damage site: open or close? Curr. Opin. Cell Biol. 23: 277-83.

63. Kong, X., Stephens, J. P., Ball, Jr. A. R., Heale, J. T., Newkirk, D. A., Berns, M. W., and Yokomori, K. (2011). Condensin I recruitment to base damage-enriched DNA lesions is modulated by PARP1. PLoS ONE 6: e23548. PMC3155556

64. Chien, R., Zeng, W., Ball, Jr., A. R., and Yokomori, K. (2011). Cohesin: a critical chromatin organizer in mammalian gene regulation. Biochemistry and Cell Biol. 89:445-58.

65. Newkirk, D., Biesinger, J., Chon, A., Yokomori, K., and Xie, X. (2011). AREM: aligning short reads from ChIP-sequencing by expectation maximization. J. Comput. Biol. 18:1495-505. PMC3216101

66. Zeng, W., Ball, Jr., A. R., and Yokomori, K. (2012). The epigenetics of facioscapulohumeral muscular dystrophy. A book chapter in "Epigenomics: From Chromatin Biology to Therapeutics”. Ed. Appasani, K. Cambridge University Press. ISBN: 9781107003828.

68. Wu, N., Kong, X., Ji, Z., Zeng, W., Potts, P. R., Yokomori, K., Yu, H. (2012). Scc1 sumoylation by Mms21 promotes sister chromatid recombination through counteracting Wapl. Genes Dev. 26:1473-85. PMC3403015

70. Ball, Jr. A. R., Chen, Y.-Y., and Yokomori, K. (2014). Mechanisms of cohesin-mediated gene regulation and lessons learned from cohesinopathies. BBA-Gene Regulatory Mechanisms. 1839: 191-202.

71. Kong, X., Ball, Jr., A. R., Pham, H. X., Zeng, W., Chen, H.-Y., Schmiesing, J. A., Kim, J.-S., Berns, M., and Yokomori, K. (2014). Distinct functions of human cohesin-SA1 and cohesin-SA2 in DNA double-strand break repair. Mol. Cell. Biol. 34: 685-98.

72. Hinde, E., Yokomori, K., Gaus, K., Hahn, K. M., Gratton, E. (2014). Fluctuation-based imaging of nuclear Rac1 activation by protein oligomerisation. Sci. Rep. 4:4219. doi: 10.1038/srep04219.

73. Zeng, W.,* Chen, Y.-Y.,* Newkirk, D. A., Wu, B., Balog, J., Kong, X., Ball, Jr., A. R., Zanotti, S., Tawil, R., Hashimoto, N., Mortazavi, A., van der Maarel, S., and Yokomori, K. (2014). Genetic and epigenetic characteristics of FSHD-associated 4q and 10q D4Z4 that are distinct from non-4q/10q D4Z4 homologs. Hum. Mutat. 35:998-1010. (*co-first authors).

74. Hinde, E.,* Kong, X., Yokomori, K.,* Gratton, E. (2014). Chromatin dynamics during DNA repair revealed by pair correlation analysis of molecular flow in the nucleus. Biophys. J. 107:55-65. (*co-corresponding authors).

75. Tuzon, C. T., Spektor, T., Kong, X., Congdon, L. M., Wu, S., Schotta, G., Yokomori, K., Rice, J. C. (2014). Concerted activities of distinct H4K20 methyltransferases at DNA double-strand breaks regulate 53BP1 nucleation and NHEJ-directed repair Cell Reports 8:430-8. PMC4134327

76. Silva, B. A., Stambaugh, J. R., Yokomori, K.,* Shah, J.I V.*, and Berns, M. W.* (2014). DNA damage to a single chromosome end delays anaphase onset. J. Biol. Chem. 289:22771-84. (*co-corresponding authors).

77. Spitler, R., Ho, H., Norpetlian, F., Kong, X., Jiang, J., Yokomori, K., Andersen, B., Boss, G. R., Berns, M. W. (2015). Combination of low level light therapy and nitrosyl-cobinamide accelerates wound healing. J. Biomed. Opt. 20: 51022.
  78. Cruz, G. M. S.,* Kong, X.,* Silva, B. A.,* Khatibzadeh, N., Thai, R., Berns, M. W,§ and Yokomori, K.§ (2016). Femtosecond near-infrared laser microirradiation reveals a crucial role for PARP signaling on factor assemblies at DNA damage sites. Nucleic Acids Res. 44:e27. (*co-first authors; §co-corresponding authors).
  79. Kong, X., Ball, Jr., A. R., and Yokomori, K. (2016). The use of laser microirradiation to investigate the roles of cohesins in DNA repair. Methods. Mol. Biol. (in press).
Grant NIH, FSH Society
Other Experience The Institutional Biosafety Committee Chair
UCI 2007—2011

Graduate Advisor
Dept. Biol. Chem. 2000—pres

Graduate Programs Cellular and Molecular Biosciences

Mathematical and Computational Biology

Research Centers CFCCC Cancer Research Institute
Center for Complex Biological Systems
Center for Epigenetics and Metabolism
Developmental Biology Center
Institute for Genomics and Bioinformatics
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Last updated 04/25/2016