ProfessorOffice: MRB 381Phone: 970-491-5440Website: http://hansenlab.bmb.colostate.eduEducation: Ph.D., University of Wisconsin-MadisonEmail: email@example.comResearch Title: Higher Order Chromatin Structure and Chromatin Architectural Proteins
Folding of the chromatin fiber into higher order secondary and tertiary chromatin structures is intimately linked to nuclear functions such as transcription, replication, and DNA repair. The focus of my research falls into two distinct areas: the intrinsic dynamics of chromatin fibers in solution, and characterization of chromatin architectural proteins and their effects on secondary and tertiary chromatin structures. Both projects are heavily dependent on the techniques of analytical ultracentrifugation and agarose multigel electrophoresis to provide quantitative analyses of complex macromolecular assemblages in solution.
The intrinsic conformational dynamics of the chromatin fiber are dictated by the core histone N-terminal tail domains and a family of proteins called linker histones. We are expressing and purifying recombinant core histone and linker histone mutants and and using them to assemble biochemically defined chromatin model systems in vitro to better understand how these proteins affect the higher order structure and stability of the chromatin fiber.
Our studies of chromatin architectural proteins focus on yeast silencing proteins (SIR2, SIR3 and SIR4), and human MeCP2. The SIR proteins interact with themselves and chromatin to form transcriptionally silenced heterochromatin. We are currently dissecting the mechanisms and determinants of the protein-protein and protein-chromatin interactions involved in SIR-dependent formation of heterochromatin in vitro. MeCP2 is a methyl DNA binding protein that also possesses a remarkably potent ability to condense chromatin fibers into unique secondary and tertiary chromatin structures. Mutations in MeCP2 are causative of the neurological disorder, Rett Syndrome, and we are very interested in characterizing the mechanisms involved in native and mutant MeCP2 interaction with chromatin, and the resulting supramolecular chromatin structures formed by such interactions.
Lu X., Hamkalo B., Parseghian M.H., Hansen J.C. (2009)Chromatin Condensing Functions of the Linker Histone C-Terminal Domain Are Mediated by Specific Amino Acid Composition and Intrinsic Protein Disorder. Biochemistry, 48, 164-72
Adkins N.L., McBryant S.J., Johnson C.N., Leidy J.M., Woodcock C.L., Robert C.H., Hansen J.C., Georgel P.T. (2009) Role of nucleic acid binding in Sir3p-dependent interactions with chromatin fibers. Biochemistry 48, 276-88.
Hite, K., Adams, V.A., and Hansen, J.C. (2009) Recent advances in MeCP2 structure and function. Biochem. Cell Biol. 87, 219-27.
McBryant,S.J., Klonoski, K., Williams, S., Resch, M.E., Toombs, J.A., III, Hobdey, S.E., and Hansen, J.C. (2009) Functional determinants of histone H4 N-terminal domain action during nucleosomal array oligomerization: role of amino acid sequence, domain length, and charge density. J. Biol. Chem. 284, 16716-22.
McBryant, S.M., Krause, C., Woodcock, C.L. and Hansen, J.C. (2008) The silent information regulator 3 protein, SIR3p, binds to chromatin fibers and assembles a hypercondensed chromatin architecture in the presence of salt. Mol. Cell. Biol. 28, 3563-72. Epub 2008 Mar 24.
Lu, X., Chodaparambil, J.V., Simon, M.D., Hansen, J.C., Shokat, K.M.and Luger, K. (2008) The effect of H3 K79 dimethylation and H4 K20 trimethylation on nucleosome and chromatin structure. Nature Str. Mol. Biol. 15, 1122-4. Epub 2008 Sep 14.
Fuxreiter M., Tompa P., Simon I., Uversky V.N., Hansen J.C., Asturias F.J. (2008) Malleable machines take shape in eukaryotic transcriptional regulation. Nature Chem. Biol. 4, 728-37.
Lu, X.,Chodaparambil, J.V., Barbera, A.J., Kay, K.M., Hansen, J.C., and Luger, K. (2007) A charged and contoured surface on the nucleosome regulates chromatin compaction. Nature Str. Mol. Biol., 14, 1107-07.
Nikitina, T, Shi, X. Gosh, R.P., Horowitz- Scherer, R.A., Hansen, J.C., Grigoryev, S., and Woodcock, C.L. (2007) MeCP2-chromatin interactions include the formation of chromatosome-like structures and are altered in mutations Causing Rett Syndrome. J. Biol. Chem. 282, 28237-45. Epub 2007 Jul 27
Chodaparambil, J.V., Lu, X.,Barbera, A.J., Kay, K.M., Hansen, J.C., and Luger, K. (2007) A charged and contoured surface on the nucleosome regulates chromatin compaction. Nature Str. Mol. Biol., 14, 1107-07.
Berndsen, CE, Selleck, W, McBryant SJ, Hansen, J.C., Tan, S, and Denu, JM (2007) Nucleosome Recognition by the Piccolo NuA4 Histone Acetyltransferase Complex. Biochemistry. 46, 2091-99. 2007 Feb 3; [Epub ahead of print].
Kan, P-Y., Lu, X., Hansen, J.C. and Hayes, J.J (2007) The H3 tail domain participates in multiple interactions during folding and self-association of nucleosome arrays. Mol. Cell. Biol. 46, 2084-2091 Jan 22; [Epub ahead of print].
Adams, V. A., McBryant, S.M., Wade. P.A., Woodcock, C.L. and Hansen, J.C. (2007) Intrinsic disorder and autonomous domain function in the multifunctional nuclear protein, MeCP2. J. Biol. Chem. 282, 15057-64. Mar 19; [Epub ahead of print].
Nikitina, T, Shi, X. Gosh, R.P., Horowitz- Scherer, R.A., Hansen, J.C. and Woodcock, C.L. (2007) Multiple modes of interaction between the methylated DNA binding protein MeCP2 and chromatin. Mol. Cell. Biol. 27, 864-77, Nov 13; [Epub ahead of print]
McBryant, S.M., Krause, C., and Hansen, J.C. (2006) Domain Organization and Quaternary Structure of the S. cerevisiae Silent Information Regulator 3 protein, SIR3p. Biochemistry 26, 15941-8.
Braemaesle, D, and Hansen, J.C. (2006) Developmental biology: holding pattern for histones. Curr. Biol. 16, R918-20.
McBryant, S.M., Adam, V., and Hansen, J.C. (2006) Chromatin architectural proteins. Chromosome Res. 14, 39-51
Hansen, J.C. (2006) Linking Genome Structure and Function Through Specific Histone Acetylation. ACS Chemical Biology. 1, 69-72.
Hansen, J.C., Lu, X., Ross, E.D., and Woody, R.W. (2006) Intrinsic Protein Disorder, Amino Acid Composition, and the Histone Terminal Domains. J. Biol. Chem. 281, 1853-6. Epub 2005 Nov 21.
Zheng, C., Lu, X. Hansen, J.C. and Hayes, J.J. (2005) Salt-dependent intra-and inter-nucleosomal interactions of the H3 tail domain in a model oligonucleosomal array. J. Biol. Chem. 280, 33552-7.
Gordon, F., Luger, K., and Hansen, J.C. (2005) The core histone N-terminal tail domains function independently and additively during salt-dependent oligomerization of nucleosomal arrays. J Biol Chem. In press. Epub ahead of print: Jul 19, 2005.
Luger, K. and Hansen, J.C. (2005) Nucleosome and Chromatin Fiber Dynamics. Curr. Opin. Strl. Biol. 15, 188-96.
P. Widlak, M. Kalinowska, M.H. Parseghian, X. Lu, J.C. Hansen, and W.T. Garrard (2005) Histone H1 Stimulates DNA Cleavage by the Apoptotic Nuclease, DNA Fragmentation Factor (DFF40/CAD), Through its Basic C-Terminal Domain. Biochemistry 44, 7871-78.