PhD, Stanford University
Within the nucleus, chromosomes and genes are spatially organized. We are interested in understanding the molecular mechanisms by which this spatial organization is achieved. As a model, we use the positioning and interchromosomal clustering of genes in budding yeast. Hundreds of active genes are targeted to the nuclear periphery through a physical interaction with the nuclear pore complex. This targeting is mediated by the binding of transcription factors to cis-acting elements that we have termed DNA zip codes. DNA zip codes are both necessary and sufficient for peripheral targeting and the physical interaction with the nuclear pore. Also, genes that share zip codes cluster together, whereas genes with different zip codes do not. This suggests that genomes encode their spatial organization.
Current projects are focused on:
- Understanding the molecular mechanisms by which DNA zip codes facilitate compartmentalization of the yeast genome.
- Defining the role of gene-nuclear pore interactions in promoting transcription.
- Defining the molecular mechanism of epigenetic transcriptional memory. This is a widespread and conserved mechanism by which genes, when repressed, continue to interact with the nuclear pore, poised for re-activation, for several generations.
Ahmed, S., D. G. Brickner, W. H. Light, M. McDonough, I. Cajigas, A. Froyshteter, T. Volpe and J.H. Brickner (2010). DNA zip codes control an ancient mechanism for gene targeting to the nuclear periphery. Nat. Cell Biol. 12 (2): 111-118.
Light, W., D. G. Brickner, V. Brand and J.H. Brickner (2010). Interaction of a DNA zip code with the nuclear pore complex promotes H2A.Z incorporation and INO1 transcriptional memory. Mol. Cell 40: 112-125.
Brickner, D. G. and J.H. Brickner (2010). Cdk phosphorylation of a nucleoporin controls gene localization through the cell cycle. Mol. Biol. Cell 21:3421-3432.
Brickner, D.G., S. Ahmed, L. Meldi, A. Thompson, W. Light, M. Young, T.L. Hickman, F. Chu, E. Fabre and J.H. Brickner (2012).Transcription factor binding to a DNA zip code controls interchromosomal clustering at the nuclear periphery. Dev. Cell 22: 1234-1246.
Light, W., J. Freaney, V. Sood, A. Thompson, A. D’Urso, C. Horvath and J.H. Brickner (2013). A conserved role for human Nup98 in altering chromatin structure and promoting epigenetic transcriptional memory. PLoS Biology 11:e1001524.
Brickner, D.G., R. Coukos and J.H. Brickner (2015). INO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering. Microbial Cell, 2(12): 481-490. PMC4682904
Randise-Hinchliff, C., R. Coukos, V. Sood, M. C. Sumner, S. Zdraljevic, L. Meldi Sholl, D.G. Brickner, S. Ahmed, L. Watchmaker and J.H. Brickner (2016). Strategies to regulate transcription factor-mediated gene positioning and interchromosomal clustering at the nuclear periphery. J. Cell Biol. 212(6): 633-646. PMC4792077