Vaughn Jackson, Ph.D.
Associate Professor
Dr. Jackson received his Doctorate degree in Biochemistry at the University of Iowa in 1972. His postdoctoral research was at the University of Iowa from 1972 to 1976 and at the MRC Lab of Molecular Biology, Cambridge, U.K. from 1976 to 1978. He was a research associate scientist at the University of Iowa from 1978 to 1982 and joined the faculty at the Medical College of Wisconsin in 1982.
Contact Information
jacksonv@mcw.edu
Phone: (414) 456-8776
Fax: (414) 456-6510
Research Interests
Transcription within a eucaryotic cell is not a process in which RNA polymerase can freely access the DNA for either initiation or elongation of the transcript. The DNA is associated with highly basic proteins called histones which function to condense the DNA in an organized manner and to facilitate accessibility of the DNA under regulated conditions. Four of these histones, H3, H2A, H2B, H4 coil the DNA into a left-handed supercoil and form a particle called a nucleosome. The DNA is organized into a tandem array of these nucleosomes. Because of the strong binding energies between these proteins and DNA, specific cellular mechanisms are required to access DNA for transcription or replication. We are involved in a characterization of the following potential mechanisms:
1. The role of metabolic modifications such as acetylation. A common characteristic of active genes is the presence of histones that are highly acetylated.
2. The role of topological stress in DNA. A characteristic of the transcriptional process is the formation of positive stress in advance of the RNA polymerase and negative stress in its wake.
3. The role of accessory proteins in modulating histone-DNA interactions. Several recently characterized proteins have been shown to function in either an ATP dependent or independent process to disrupt these interactions.
The figure illustrates a model of transcription which encompasses these three potential mechanisms. Laboratory procedures for testing this model involve both in vivo and in vitro experimentation. The in vivo procedures require exposure of tissue culture cells to radioactive and or density-labeled precursors in order to label proteins and or DNA under conditions which alter either replication or transcription. The dynamics of histone-DNA interactions can be studied by this approach. The in vitro procedures involve the assembly of individual components into a well defined transcription system that is designed to minimize variables. By a manipulation of the in vitro conditions, it is possible to simulate the in vivo observations. In this way, we are able to study specific regulatory mechanism in detail.
Selected Publications
"NAP1 Catalyzes the Formation of either Positive or Negative Supercoils on DNA on Basis of the Dimer - Tetramer Equilibrium of Histones H3/H4.", S. Peterson, R. Danowit, A. Wunsch and V. Jackson. Biochemistry, 46: 8634-8646 (2007)
"Histone Release during Transcription: Acetylation Stabilizes the Interaction of the H2A-H2B Dimer with the H3-H4 Tetramer in Nucleosomes that are on Highly Positively Coiled DNA", A. Wunsch and V. Jackson Biochemistry, 44(49):16351-16364. (2005)
"Histone Release during Transcription: Displacement of the Two H2A-H2B Dimers from the Nucleosome is Dependent on Different Levels of Transcription-induced Topological Stress", V. Levchenko, B. Jackson and V. Jackson Biochemistry, 44: 5357-72. (2005)
"Histone release during transcription: NAP1 forms a complex with H2A-H2B and facilitates a topologically-dependent release of H3-H4 from the nuclesome.", V. Levchenko and V. Jackson Biochemistry, 43: 2359-72. (2004)
"Chromatin Structure: State-of-the-Art': What happens to Nuclesomes during Transcripting" in Comprehensive Biochemistry, vol 39, chapter 17, V. Jackson Elshevier Publishing, (2004)
"In vitro studies on the maintenance of transcription-induced stress by histones and polyamines.", H.F. Peng and V. Jackson, J Biol Chem, 275(1), 657-668 (2000)
"Formaldehyde cross-linking for studying nucleosomal dynamics.", V. Jackson, Methods, 17(2): 125-139 (1999)
"A Measurement of the Frequency of Histone Displacement During the in vitro Transcription of Nucleosomes: RNA is a Competitor for These Histones", H.F. Peng and V. Jackson, Biochemistry, 36: 12371-12382 (1997).
"Effects of Spermine and its Cytotoxic Analogs on Nucleosome Formation on Topologically Stressed DNA in vitro", H.S. Basu, I.V. Smirnov, H.F. Peng, K. Tiffany and V. Jackson, Eur. J. Biochem., 243: 247-258 (1997).
"Preferential Binding of Histones H3 and H4 to Highly Positively Coiled DNA", V. Jackson, Biochemistry 34: 10607-10619 (1995).
"The rapid transfer and selective association of histones H2A and H2B onto negatively coiled DNA at physiological ionic strength.", W. Brooks, V. Jackson. J Biol Chem, 269(27): 18155-18166 (1994)
"Dynamics of the Interactions of Histones, H2A,H2B, and H3,H4 with Torsionally Stressed DNA", S. Jackson, W. Brooks, and V. Jackson, Biochemistry 33: 5392-5403 (1994).
"Influence of positive stress on nucleosome assembly.", V. Jackson, Biochemistry, 32(22): 5901-5912 (1993)
"In vitro evidence that transcription-induced stress causes nucleosome dissolution and regeneration." P. Pfaffle, V. Gerlach, L. Bunzel, V. Jackson. J Biol Chem, 265(28): 16830-16840 (1990)
"Studies on rates of nucleosome formation with DNA under stress.", P. Pfaffle, V. Jackson. J Biol Chem, 265(28): 16821-16829 (1990)
"In vivo studies on the dynamics of histone-DNA interaction: evidence for nucleosome dissolution during replication and transcription and a low level of dissolution independent of both.", V. Jackson. Biochemistry, 29(3): 719-731 (1990)