Faculty
Jonathan Widom , PhD
Professor
Biochemistry, Molecular Biology and Cell Biology
PhD, Stanford
Email: j-widom@northwestern.edu
Phone: (847) 467-1887
Fax: (847) 467-1380
Room: Cook Rm 4129
Research Interests
Structure and function of chromosomes, biophysical chemistry of proteins and nucleic acids
Our research is focused on the structure and function of chromosomes and related protein-DNA complexes. The long-term aims of the work are to elucidate the molecular architecture of chromosomes, the mechanisms whereby cells regulate their chromosome structure during the cell cycle, and the relationships of chromosome structure to chromosome function.
We are currently attacking four broadly important questions of topics concerning chromosome function. Three of these are: (a) How do gene-regulatory proteins gain access to their DNA target sites in chromatin? (b) How are RNA and DNA polymerase able to elongate through their natural substrates, which are chromatin, not naked DNA? (c) In what ways are genomic DNA sequences evolved or constrained to facilitate their own packaging into nucleosomes, or to contribute to gene regulation through effects on nucleosome positioning or stability?
Our research in these areas has been predominantly carried our in vitro, on chromatin fragments reconstituted from purified components, using diverse biophysical and biochemical approaches. The advanced instrumentation available in our new Keck Biophysics Facility now makes possible a wealth of exciting new biophysical approaches to these problems. In complementary new studies, we are carrying out experiments in vivo to test remarkable predictions that arise from the in vitro studies of regulatory protein binding and of nucleosome-positioning DNA sequences.
Finally, in a new project, we are working to answer fundamental questions concerning the physico-chemical basis of gene regulation, through quantitative studies on single living cells.
Selected Publications
Dynamics and function of compact nucleosome arrays. Poirier MG, Oh E, Tims HS, Widom J. Nat Struct Mol Biol. 2009 Sep;16(9):938-44. Epub 2009 Aug 23.
What controls nucleosome positions? Segal E, Widom J. Trends Genet. 2009 Aug;25(8):335-43. Epub 2009 Jul 10.
From DNA sequence to transcriptional behaviour: a quantitative approach. Segal E, Widom J. Nat Rev Genet. 2009 Jul;10(7):443-56.
Poly(dA:dT) tracts: major determinants of nucleosome organization. Segal E, Widom J. Curr Opin Struct Biol. 2009 Feb;19(1):65-71. Epub 2009 Feb 7.
Preferentially quantized linker DNA lengths in Saccharomyces cerevisiae. Wang JP, Fondufe-Mittendorf Y, Xi L, Tsai GF, Segal E, Widom J. PLoS Comput Biol. 2008 Sep 12;4(9):e1000175.
Nucleosome switches. Schwab DJ, Bruinsma RF, Rudnick J, Widom J. Phys Rev Lett. 2008 Jun 6;100(22):228105. Epub 2008 Jun 6.
Spontaneous access to DNA target sites in folded chromatin fibers. Poirier MG, Bussiek M, Langowski J, Widom J. J Mol Biol. 2008 Jun 13;379(4):772-86. Epub 2008 Apr 16.
Stopped-flow fluorescence resonance energy transfer for analysis of nucleosome dynamics. Tims HS, Widom J. Methods. 2007 Mar;41(3):296-303.
Garcia, H.G., Grayson, P., Han, L., Inamdar, M., Kondev, J., Nelson, P.C., Phillips, R., Widom, J., and Wiggins, P.A. (2006), "Biological Consequences of Tightly Bent DNA", Biopolymers 85: 115-130.
Wiggins, P.A., van der Heijden, T., Moreno-Herrero, F., Spakowitz, A., Phillips, R., Widom, J., Dekker, C., and Nelson, P.C. (2006), "Beyond the wormlike chain: High flexibility of DNA on short lengthscales probed by atomic force microscopy", Nature Nanotechnology 1: 137-141. Featured &Views.
Segal, E., Fondufe-Mittendorf, Y., Chen, L., Thåström, A., Field, Y., Moore, I.K., Wang, J.Z., and Widom, J. (2006), "A Genomic Code for Nucleosome Positioning", Nature 442: 772-778 (full Article). Featured on cover of Nature and in News & Views, highlighted in Nature Reviews Genetics , and highlighted on front page and summarized in Science section of The New York Times , July 25, 2006, and in numerous other popular-press articles internationally. Top-ranked paper in all of biology on Faculty of 1000, September 2006. Highlighted again in Nature News Feature, (2006) 244: 259-261, and again in Nature/Nurture (Autumn, 2006) as top-most downloaded research paper from Nature over current four-month period.
Pyle, A.M. and Widom, J. (2006), "Nucleic Acids", Curr. Opin. Struct. Biol. 16: 267-269.
View all publications by Jonathan Widom listed in the National Library of Medicine (PubMed). Past and current IBiS students in blue