Ph.D., University of California, Berkeley, 1995
transcriptional regulation of developmental transitions; role of chromatin remodeling in inducible gene expression
Developmental transition to reproductive development
My lab is interested in understanding at the molecular level the complex changes that occur when an organism switches developmental programs. Specifically, we investigate the transition from vegetative to reproductive development in the plant model system Arabidopsis thaliana. This transition is not only vital, important for species survival, but also a great example of a master regulator reprogramming cell fate. In addition, the switch to flower formation has important implications for plant breeding and biofuel production. Because of its central importance, many external signals (such as temperature and day length) as well as internal cues input into the timing of reproductive development. Upon perception of the required inductive signals cells at the flanks of the stem-cell-pool containing shoot apical meristem give rise to flowers instead of leaves and secondary stems. Many of our studies of this transition have focussed on the flower program master regulator and plant specific helix-turn-helix transcription factor LEAFY.
Chromatin remodeling and inducible gene expression
We are interested in chromatin regulators critical for cell identity and response to exogenous cues, including the SWI2/SNF2 subgroup chromatin remodeling ATPases. In plants there are three evolutionarily conserved SWI2/SNF2 subgroup ATPases called SPLAYED, BRAHMA and MINU. These proteins are central subunits of large multi-protein complexes that regulate stage- or tissue-specific transcription in the context of chromatin. These enzymes remodel chromatin to alter the accessibility of the DNA to transcription factors or to the transcriptional machinery by inducing non-covalent, local changes in the DNA-nucleosome association in promoter regions. Since most chromatin remodeling mutants in other higher eukaryotes are embryonic lethal, Arabidopsis provides a new entry point to genetic investigation of this process in multicellular organisms. Chromatin remodeling complexes have intrinsic tumor suppressor activity and regulate expression of other tumor suppressors. Thus elucidating the in vivo role of these ATPases is of critical importance. We are studying the roles of the SWI2/SNF2ATPases in pluripotency and differentiation and in response to endogenous (hormaonal) and exogenous (abiotic or biotic) cues. We recently found that SWI2/SNF2 subgroup ATPases act antagonistically to Polycomb repressive complexes in activation of expression of the floral homeotic genes.
We use a wide range of approches including genetics (forward and reverse genetics), genomics (ChIPseq, MNAseq and transcriptomics), biochemical approaches (proteomics, interactome screens), cell biological approaches (live imaging).
Current and Future Research Projects
1. Integration of known and novel signals at the LEAFY promoter in Arabidopsis and the Brassicaceae.
2. Regulation of flower development with emphasis on flower primordium initiation, meristem development and patterning.
3. Biological roles and regulation of activity of SWI/SNF ATPases.
4. Identification of plant Polycomb response elements, cis regulatory domains that recruit Polycomb Repressive Complexes.
Efroni, I., Han, S.K., Kim, H.J., Wu, M.F., Sang, Y., Steiner, E., Hong, J.C., Eshed, Y*., and Wagner, D*. (in press). Regulation of leaf maturation by chromatin-mediated modulation of cytokinin responses. Developmental Cell 24, 438-445. * corresponding authors
Yamaguchi, N., Wu, M.-F., Winter, C., Berns, M., Nole-Wilson, S., Yamaguchi, A., Coupland, G., Krizek, B., and Wagner, D. (2013). A Molecular Framework for Auxin-mediated Initiation of Flower Primordia. Developmental Cell 24, 1–12.
Han, S.K., Sang, Y., Rodrigues, A., BIOL425F2010, Wu, M.F., Rodriquez, P.L. and Wagner, D. (2012). The SWI2/SNF2 chromatin remodeling ATPase BRAHMA represses Abscisic Acid Responses in the Absence of the Stress Stimulus in Arabidopsis. Plant Cell 2012;24 4892-4906.
Sang, Y., Silva-Ortega,
C.O., Wu, S., Wu, M.-F., Pfluger, J., Gillmor, C.S., Gallagher, K.*, and Wagner, D*. (2012) Two non-canonical
SWI2/SNF2 chromatin remodeling ATPases redundantly control embryogenesis and
stem cell maintenance. The Plant Journal 72, 1000-1014. * corresponding authors
EPIC Planning Committee (2012) (Wagner D. corresponding author). Reading the second Code: Mapping Epigenomes to understand Plant Growth, Development and Adaptation to the Environment. Plant Cell 24 (6) 2257-2261.
Yamaguchi, N., Yamaguchi, A., Abe, M., Wagner, D., and Komeda, Y. (2012). LEAFY controls Arabidopsis pedicel length and orientation by affecting adaxial-abaxial cell fate. Plant Journal 69, 844-856.
Wu, M.F., Sang, Y., Bezhani, S., Yamaguchi, N., Han, S.K., Li, Z., Su, Y., Slewinski, T.L., and Wagner, D. (2012). SWI2/SNF2 chromatin remodeling ATPases overcome polycomb repression and control floral organ identity with the LEAFY and SEPALLATA3 transcription factors. Proceedings of the National Academy of Sciences of the United States of America 109, 3576-3581.
Pastore, J.J., Limpuangthip, A., Yamaguchi, N., Wu, M.F., Sang, Y., Han, S.K., Malaspina, L., Chavdaroff, N., Yamaguchi, A., and Wagner, D. (2011). LATE MERISTEM IDENTITY2 acts together with LEAFY to activate APETALA1. Development 138, 3189-3198.
Winter, C.M., Austin, R.S., Blanvillain-Baufume, S., Reback, M.A., Monniaux, M., Wu, M.F., Sang, Y., Yamaguchi, A., Yamaguchi, N., Parker, J.E., J.E., Parcy, F., Jensen, S.T., Li, H., Wagner, D. (2011). LEAFY Target Genes Reveal Floral Regulatory Logic, cis Motifs, and a Link to Biotic Stimulus Response. Developmental Cell 20, 430-443. For data visualization see: http://gbrowse.genomics.upenn.edu/cgi-bin/gbrowse/tair8/
Wagner, D.*, and Meyerowitz, E. (2011). Switching on flowers: transient LEAFY induction reveals novel aspects of flower development in Arabidopsis. Frontiers in Plant Science 2:60. * corresponding author
Wagner, D. (2009) Flower morphogenesis: timing is key. Developmental Cell 16(5): 621-622.
Yamaguchi A, Wu MF, Yang L, Wu G, Poethig RS and Wagner, D. (2009) The microRNA-regulated SBP-Box transcription factor SPL3 is a direct upstream activator of LEAFY, FRUITFULL, and APETALA1. Developmental Cell 17(2): 268-278.
Sang Y, Wu MF, Wagner D. (2009) The stem cell-Chromatin connection. Seminars in Cell & Developmental Biology.
Walley JW, Rowe HC, Xiao Y, Chehab EW, Kliebenstein DJ, Wagner, D., Dehesh, K. (2008) The chromatin remodeler SPLAYED regulates specific stress signaling pathways. PLoS Pathogens 4(12): e1000237.
Pfluger, J., and Wagner, D. (2007). Histone modifications and dynamic regulation of genome accessibility in plants. Curr Opin Plant Biol. (6) 645-52.
Bezhani, S., Winter, C., Hershman, S., Wagner, J.D., Kennedy, J.F., Kwon, C.S., Pfluger, J., Su, Y., and Wagner, D. (2007). Unique, Shared, and Redundant Roles for the Arabidopsis SWI/SNF Chromatin Remodeling ATPases BRAHMA and SPLAYED. Plant Cell 19, 403-416.
Kwon, C.S., and Wagner, D. (2007). Unwinding chromatin for development and growth: a few genes at a time. Trends Genet. (8): 403-12.
Kwon, C.S., Hibara, K.I., Pfluger, J., Bezhani, S., Metha, H., Aida, M., Tasaka, M., and Wagner, D. 2006. A role for chromatin remodeling in regulation of CUC gene expression in the Arabidopsis cotyledon boundary. Development 133 (3223-3230).
Saddic, L.A., Huvermann, B., Bezhani, S., Su, Y., Winter, C.M., Kwon, C.S., Collum, R.P. and Wagner, D. (2006) The LEAFY target LMI1 is a meristem identity regulator and acts together with LEAFY to regulate expression of CAULIFLOWER. Development, 133, 1673-1682.
Su, Y., Kwon, C. S., Bezhani, S., Huvermann, B., Chen, C., Peragine, A., Kennedy, J. F. and Wagner, D. (2006). The N-terminal ATPase AT-hook-containing region of the Arabidopsis chromatin-remodeling protein SPLAYED is sufficient for biological activity. Plant J 46, 685-99.
Kwon, C.S., Chen, C., and Wagner, D. (2005). WUSCHEL is a primary target for transcriptional regulation by SPLAYED in dynamic control of stem cell fate in Arabidopsis. Genes Dev 19, 992-1003.
Wagner, D. , Wellmer, F., Dilks, K., William, D.A., Smith, M.R., Kumar, P.P., Riechmann, J.L., Greenland, A.J. and Meyerowitz, E.M. (2004) Floral Induction in Tissue Culture: a System for the Analysis of LEAFY-Dependent Gene Regulation, Plant J. 39, 273-282.
William, D.A., Su, Y., Smith, M.R., Lu, M.,Baldwin, D.A. And Wagner, D. (2004) Genomic Identification of direct target genes of LEAFY, Proc Natl Acad Sci U S A 101, 1775-1780.
Wagner, D. 2003. Chromatin regulation of plant development. Curr Opin Plant Biol 6, 20-28.
Wagner, D. and E.M. Meyerowitz, 2002. SPLAYED, a Novel SWI/SNF ATPase Homolog, Controls Reproductive Development in Arabidopsis. Current Biology, 2002. 12 (2): p. 85-94.
Wagner, D., R.W. Sablowski, and E.M. Meyerowitz, (1999) Transcriptional activation of APETALA1 by LEAFY. Science, 285(5427): p. 582-4.
BIOL 255: Plant Biology
BIOL 483: Epigenetics
BIOL 700: Advanced Topics in Current Biology Research