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Xing Dai

Professor, Biological Chemistry
School of Medicine

PH.D., University of Chicago

Phone: (949) 824-3101
Fax: (949) 824-2688
Email: xdai@uci.edu

University of California, Irvine
D234 Med Sci I
Mail Code: 1700
Irvine, CA 92697

Skin and mammary stem cells, Wnt signaling, chromatin, transcription
URL www.ucihs.uci.edu/biochem/faculty/dai.htm
1992 NIH Biotechnology Pre-doctoral Training Grant Award
1995 Departmental award for outstanding performance in the field of Biochemistry and Molecular Biology at the University of Chicago (generally known as the “best thesis award”)
1995 Howard Hughes Medical Institute Postdoctoral Fellowship
1996 NIH Individual National Research Service Award
2001 March of Dimes Basil O'Connor Award
2004 NIAMS/NIH Independent Scientist Award
2005 UCI Faculty Career Development Travel Award
2006,2007,2008 UCI School of Medicine Excellence in Teaching Award
Appointments 1987-1989 Research Assistant, Department of Biochemistry and Biophysics, University of Hawaii, Honolulu, HI
1989-1990 Teaching Assistant, Dept. of Biochemistry and Molecular Biology, University of Chicago, IL
1989-1992 Research Assistant, Dept. of Molecular Genetics and Cell Biology, University of Chicago, IL
1992-1995 NIH pre-doctoral trainee, Dept. of Biochemistry and Molecular Biology, University of Chicago, IL
1995-1999 Postdoctoral Fellow, Dept. of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, University of Chicago, IL
1999-2006 Assistant Professor, Dept. of Biological Chemistry, University of California, Irvine,
2006-2011 Associate Professor, Dept. of Biological Chemistry, University of California, Irvine
2011- Professor, Dept. of Biological Chemistry, University of California, Irvine
The development, maintenance, and regeneration of complex mammalian tissues involve multi-tiered control mechanisms including those regulating commitment to different cell lineages and self-renewal/proliferation/differentiation along a particular lineage. Regenerative tissues such as skin and mammary gland are excellent model systems to study the genetic pathways underlying such control mechanisms, as they contain stem cells that persist throughout the life span of an animal and possess self-renewal and differentiation potential. Our long-term goal is to understand the transcriptional and chromatin control of epithelial stem cell self-renewal and differentiation, and to gain insights into how mis-regulation can result in diseased conditions including skin and breast cancer.
We study two families of transcription/chromatin regulators, namely Ovol zinc finger proteins and Pygopus PHD finger proteins using a combinatory approach involving mouse genetics, developmental biology, biochemistry, molecular biology, and cell biology. Work from us as well as others has shown that these proteins are either regulated by, or directly participate in, important developmental signaling pathways such as Wnt-beta-catenin-LEF/TCF and TGFbeta/BMP, and act at least in part through regulating gene transcription and histone modifications.
Ovol proteins - We have shown using knockout mouse and cell culture models that Ovol1 is required for developmental epithelial progenitor cells to exit proliferation so they can terminally differentiate. Our molecular analysis has shown that it does so by recruiting histone deacetylases and regulating key cell cycle genes including c-Myc and Id2. Our current research addresses the function of Ovol2 in skin and mammary epithelial stem cell development and differentiation, as well as how it performs its function at a molecular level.
Pygopus proteins - We have shown that Pygopus 2 (Pygo2) converges with Wnt signaling to regulate multiple developmental processes including that of skin hair follicle and mammary gland. We have uncovered a critical role for Pygo2 in regulating the expansion of mammary epithelial stem/progenitor cells, via "reading" and "writing" histone H3 K4 trimethylation, a specific type of histone code that is associated with active chromatin. Our current studies focus on the identification of Pygo2 targets and interacting proteins, as well as on the involvement of Pygo2 in breast tumorigenesis
Publications Watanabe, K., Villarreal-Ponce, A., Sun, P., Salmans, M. L., Fallahi, M., Andersen, B., and Dai, X. (2014) Mammary morphogenesis and regeneration require the inhibition of epithelial-to-mesenchymal transition by Ovol2 transcriptional repressor. Developmental Cell, 29(1):47-58.
  Lee, B., Villarreal-Ponce, A., Fallahi, M., Ovadia, J., Sun, P., Yu, Q.-C., Ito, S., Sinha, S., Nie, Q., and Dai, X. (2014) Transcriptional mechanisms link epithelial plasticity to adhesion and differentiation of epidermal progenitor cells. Developmental Cell. 29(1):59-74
  Gu, B., Watanabe, K., Sun, P., Fallahi, M., and Dai, X. (2013). Chromatin effector Pygo2 mediates Wnt-Notch cross-talk to suppress luminal/alveolar potential of mammary stem and basal cells. Cell Stem Cell, 13(1):48-61.
  Watanabe, K., Fallahi, M., and Dai, X. (2013). Chromatin effector Pygo2 regulates mammary tumor initiation and heterogeneity in MMTV-Wnt1 mice. Oncogene. Jan 21.
  Gu, B., Watanabe, K., and Dai, X. (2012) Pygo2 regulates histone gene expression and H3 K56 acetylation in human mammary epithelial cells. Cell Cycle 11(1):79-87
  Gu, B., Sun, P., Yuan, Y., Moraes, R., Li, A., Teng A., Agrawal, A., Rhéaume, C., Bilanchone, B., Veltmaat J. M, Takemaru, K., Millar, S. Lee, E. Y-H. P., Lewis, M. T., Li, B., and Dai, X. (2009). Pygo2 expands mammary progenitor cells by regulating histone H3 K4 methylation. J. Cell Biology 185:811-26. (Chosen for news and commentary).
  Wells, J., Lee, B., Cai, A. Q., Karapetyan, A., Lee, W. J., Rugg, E., Sinha, S., Nie, Q., Dai, X. (2009). Ovol2 suppresses cell cycling and terminal differentiation of keratinocytes by directly repressing c-Myc and Notch1. J. of Biological Chemistry 284(42):29125-35.
  Nair M., Nagamori, I., Sun, P., Mishra, D., Rhéaume, C., Li, B., Sassoni-Corssi P., Dai, X. (2008). Nuclear regulator PYGO2 controls spermiogenesis and chromatin modification. Developmental Biology 320(2):446-55.
  Jonckheere, N., Mayes, E.; Shih, H. P.; Li, B., Lioubinski, O., Dai., X., and Sander, M. (2008). Analysis of mPygo2 mutant mice suggests a requirement for mesenchymal Wnt signaling in pancreatic growth and differentiation. Developmental Biology, 318(2):224-35.
  Nair, M. Bilanchone, V., Ortt, K., Sinha, S., and Dai, X. (2007). Ovol1 represses transcription by competing for DNA binding with the c-Myb activator and by recruiting histone deacetylases. Nucleic Acids Research 35, 1687-1697.
  Qian, D., Jones, C., Rzadzinska, A., Mark, S., Zhang, X., Steel, K.P., Dai, X., and Chen, P. (2007). Wnt5a functions in planar cell polarity regulation in mice. Developmental Biology 306, 121-133.
  Nair, M., Teng, A., Bilanchone, V., Agrawal, A., Li, B. and Dai, X. (2006). Ovol1 regulates the growth arrest of embryonic epidermal progenitor cells and represses c-Myc transcription. J. Cell Biology 173, 253-264.
  Mackay, D. R., Hu, M., Li, B., Rhéaume, C., and Dai, X. (2006). The mouse Ovol2 gene is required for cranial neural tube development. Developmental Biology 291, 38-52.
  Li, B., Nair, M., Mackay, D. R., Bilanchone, V., Hu, M., Fallahi, M., Song, H., Dai, Q., Cohen, P. E. and Dai, X. (2005). Ovol1 regulates meiotic pachytene progression during spermatogenesis by repressing Id2 expression. Development 132, 1463-1473.
  Kaufman, C. K., Zhou, P., Pasolli, H. A., Rendl, M., Bolotin, D., Lim, K. C., Dai, X., Alegre, M. L., and Fuchs, E. (2003). GATA-3: an unexpected regulator of cell lineage determination in skin. Genes & Development 17, 2108-2122.
  Li, B., Mackay, D. R., Dai, Q., Li, T. W. H., Nair, M., Fallahi, M., Schonbaum, C., Fantes, J., Mahowald, A., Waterman, M. L., Fuchs, E., and Dai, X. (2002). The LEF1/b-catenin complex activates movo1, a mouse homolog of Drosophila ovo gene required for epidermal appendage differentiation. Proc. Natl. Acad. Sci. USA 99, 6064-6069.
  Dai, X., Schonbaum, C., Degenstein, L., Bai, W., Mahowald, A., Fuchs, E. (1998). "The ovo gene required for cutcle formation and oogenesis in flies is involved in hair formation and spermatogenesis in mice". Genes & Development 12, 3452-3463.
  Dai, X. and Rothman-Denes, L. B. (1998). "Sequence and DNA strucutral determinants of N4 virion RNA polymerase-promoter recognition". Genes & Development 12, 2782-2790.
  Dai, X., Greizerstein, M., Nadas-Chinni, K., and Rothman-Denes, L. B. (1997). "Supercoil-induced extrusion of a regulatory DNA hairpin". Proc. Natl. Acad. Sci. USA 94, 2174-2179.
  Glucksmann-Kuis, M. A., Dai, X., Markiewicz, P., and Rothman-Denes, L. B. (1996). "E. coli SSB activation of N4 virion RNA polymerase: specific activation of an essential DNA hairpin required for promoter recognition". Cell 84, 147-154.
  Ogata, K., Dai, X., and Volini, M. (1989). " Bovine mitochondrial rhodanese is a phosphoprotein". J. Biol. Chem. 264, 2718-2725.
American Society for Cell Biology
Graduate Programs Cancer Biology

Cell Biology

Developmental Biology and Genetics

Mechanisms of Gene Expression

Link to this profile http://www.faculty.uci.edu/profile.cfm?faculty_id=4552
Last updated 04/21/2014