Faculty
Jason Brickner, PhD
Assistant Professor
Biochemistry, Molecular Biology and Cell Biology
PhD, Stanford
Email: j-brickner@northwestern.edu
Phone: (847) 467-0210, (847) 467-0201
Fax: (847) 467-1380
Room: Pancoe Rm 3-105
Research Interests
A single genome can produce many different phenotypes. This is particularly clear in multicellular organisms where cells having the same genome become distinct tissues. The primary mechanism by which this is achieved is through regulated gene expression. How gene expression is controlled has been the focus of intense investigation. My lab has recently made the surprising discovery that the position of a gene within the nucleus can regulate its expression.
Our ultimate goal is to understand how the large-scale spatial organization of the nucleus is determined and how it impacts the expression of genes. We propose that gene expression can involve targeting to specific destinations within the nucleus. Targeting may promote gene expression by exploiting the existing spatial organization of proteins that are important for transcription. Indeed, the position of many genes within the nucleus changes with activation or repression. We have found that full transcription of a model gene requires relocalization from the nucleoplasm to the nuclear periphery. Localization of this gene within the nucleus is controlled by cis-acting “DNA zip codes”. These are DNA elements that are sufficient to confer a particular localization within the nucleus. We have also found that localization of genes within the nucleus can function as a form of transcriptional memory after these genes are repressed, priming them for reactivation.
Our work leads us to propose that genomes have evolved to encode signals that control their spatial organization. This spatial organization can be exploited and manipulated to influence gene expression. The next big challenge in this field will be to understand how gene-specific regulation can be integrated into the three-dimensional organization of the genome. We are currently working to understand more globally how chromosomes are spatially organized and how this influences gene expression.
Selected Publications
Gard S., W. Light, B. Xiong, T. Bose, A.J. McNairn, B. Harris, B. Fleharty, C. Seidel, J.H. Brickner, and J.L. Gerton, (2009). Cohesinopathy mutations disrupt the subnuclear organization of chromatin. J Cell Biol. 187(4): 455–462.
Brickner, J. H. (2009). Transcriptional memory at the nuclear periphery. Curr. Opin. Cell Biol. 21:1-7.
Ahmed, S. and J.H. Brickner (2007). Regulation and epigenetic control of transcription at the nuclear periphery. Trends in Genetics.
Brickner, D.G., I. Cajigas, Y. Fondufe-Mittendorf, S. Ahmed, P.-C. Lee, J. Widom and J.H. Brickner (2007). H2A.Z-mediated localization of genes at the nuclear periphery confers epigenetic memory of previous transcriptional state. PLoS 5(4): e81.
T.C. Walther*, J.H. Brickner*, P.S. Aguilar, S. Bernales, C. Pantoja and P. Walter (2006). Eisosomes mark static sites of endocytosis. Nature 439: 998-1003. *Equal contributors
Kaiser, S.E, J.H. Brickner, A.R. Reilein, T.D. Fenn, P. Walter and A.T. Brunger (2005). Structural basis of FFAT Motif-mediated ER targeting. Structure, 13(7), 1035-1045.
Gene recruitment of the activated INO1 locus to the nuclear membrane.
Brickner JH, Walter P.
PLoS Biol. 2004 Nov;2(11):e342. Epub 2004 Sep 28.
View all publications by Jason Bricknerlisted in the National Library of Medicine (PubMed).(IBiS students in blue)