Jeffrey C. Hansen
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| Hansen, Jeffrey C. - Professor |
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| Jeffrey.C.Hansen@ColoState.edu |
| Office Number: MRB 381 |
| Phone Number: (970) 491-5440 |
| Fax Number: (970) 491-0494 |
| Research Title: |
| Higher Order Chromatin Structure and Chromatin Architectural Proteins |
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| 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. |
Selected Publications: |
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. Luger, K. and Hansen, J.C. (2005) Nucleosome and Chromatin Fiber Dynamics. Curr. Opin. Strl. Biol. 15, 188-96. 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. P.A. Doucette, L.J. Whitson, X. Cao, V. Schirf, B. Demeler, J. Selverstone Valentine, J.C. Hansen, and P.J. Hart (2005) Dissociation of Human Copper-Zinc Superoxide Dismutase Dimers Using Chaotrope and Reductant: Insights into the Molecular Basis for Dimer Stability. J. Biol. Chem. 279, 54558-66. Epub ahead of print: 2004 Oct 8. Lu, X. and Hansen, J.C. (2004) Identification of Specific Functional Sub-domains Within the Linker Histone H1ยบ C-terminal Domain. J. Biol. Chem. 279, 8701-7. Epub ahead of print: 2003 Dec 10. Georgel, P.T. and Hansen, J.C. (2004) Biophysical analysis of specific genomic loci assembled as chromatin in vivo. Meth. Enzymol. 376, 17-29. Georgel P.T. and Hansen J.C. (2003) Quantitative characterization of specific genomic promoters using agarose gel electrophoresis. Biopolymers. 68, 557-562. Georgel, P.T., Horowitz- Scherer, R.A., Adkins, N., Woodcock, C.L., Wade, P.W. and Hansen, J.C. (2003) Chromatin Compaction by Human MeCP2: Assembly of Novel Secondary Chromatin Structures in the Absence of DNA Methylation. J. Biol. Chem., 278, 32181-32188. Epub 2003 Jun 04. Georgel, P.T., Fletcher, T.M., Hager G., and Hansen, J.C. (2003) Formation of Condensed Secondary and Tertiary Chromatin Structures by Genomic MMTV Promoters. Genes Dev. 17,1617-1629. Horn P.J., Carruthers L.M., Logie C., Hill D.A., Solomon M.J., Wade P.A., Imbalzano A.N., Hansen J.C., Peterson CL (2002) Phosphorylation of Linker Histones Regulates ATP-dependent Chromatin Remodeling Enzymes. Nature Str. Biol. 9, 263-267. Hansen, J.C. (2002) Conformational Dynamics of the Chromatin Fiber in Solution: Determinants, Mechanisms and Functions. Ann. Rev. Biophys. Biomol. Str. 31, 361-392. Fan, J., Gordon F, Luger K, Hansen J.C., Tremethick D.J. (2002) The Essential Histone Variant H2A.Z Regulates the Equilibrium Between Different Chromatin Conformational States Nature Str. Biol. 9, 172-176. Horn P.J., Crowley K.A., Carruthers L.M., Hansen J.C., Peterson C.L. (2002) The SIN Domain of the Histone Octamer is Essential for Intramolecular Folding of Nucleosomal Arrays. Nature Str. Biol. 9, 167-171. Georgel, P.T., Palacios DeBeer, M.A., Pietz, G., Fox, C.A. and Hansen, J.C. (2001) Sir3-dependent Assembly of Supramolecular Chromatin Structures in vitro. Proc. Natl. Acad. Sci., 98, 8584-8589. Wolffe, A.P. and Hansen, J.C. (2001) Nuclear Visions: Functional Versatility from Structural Instability. Cell 104, 631-634. Hayes, J.J. and Hansen, J.C. (2001) Nucleosomes and the Chromatin Fiber. Curr. Opin. Genet. Dev. 11, 124-129. Sendra, R., Tse, C., and Hansen, J.C. (2000) The Yeast Histone Acetyltransferase A2 Complex, but not free Gcn5p, Binds Stably to Nucleosomal Arrays. J. Biol. Chem. 275, 24928-24934. Carruthers, L.M. and Hansen, J.C. (2000) The Core Histone N-termini Function Independently of Linker Histones During Chromatin Condensation J. Biol. Chem. 275, 37285-37290. Logie, C., Tse, C., Hansen, J.C., and Peterson, C.L. (1999) The Core Histone N-terminal Domains are Required for Multiple Rounds of Catalytic Remodeling by the SWI/SNF and RSC Complexes. Biochemistry 38, 2514-2522. Pollard, K., Samuels, M.L., Crowley, K.A., Hansen, J.C., and Peterson, C.P. (1999) Functional Interaction Between GCN5 and Polyamines: a New Role for Core Histone Acetylation. EMBO J. 18, 5622-5633. Tse, C., Sera, T., Wolffe, A.W., and Hansen, J.C. (1998) Acetylation-induced Decondensation of Nucleosomal Arrays Dramatically Facilitates Transcription by RNA Polymerase III. Mol. Cell. Biol. 18, 4629-4638. Tse, C., Fletcher, T. M., and Hansen, J.C. (1998) Enhanced Transcription Factor Access to Arrays of H3/H4 Tetramer-DNA Complexes: Implications for Replication and Transcription. Proc. Natl. Acad. Sci. 95, 12169-12173. Carruthers, L.M.., Bednar, J., Woodcock, C. and Hansen, J.C. (1998) Linker Histones Stabilize the Intrinsic Salt-dependent Folding of Nucleosomal Arrays: Mechanistic Ramifications for Higher Order Chromatin Folding. Biochemistry, 37, 14776-14787. Hansen, J.C., Tse, C., and Wolffe, A.P. (1998) Structure and Function of the Core Histone N-termini: More than Meets the Eye. Biochemistry 37, 17637-17641. Bednar, J., Horowitz, R.A., Grigoryev, S.A., Carruthers, L.C., Hansen, J.C., Koster, A.J., and Woodcock, C. L. (1998) Nucleosomes, Linker DNA and Linker Histone Form a Unique Structural Motif that Directs the Higher Order Folding and Compaction of Nucleosomal Arrays. Proc. Natl. Acad. Sci. 95, 14173-14178. Tse, C., Ruiz-Garcia, A.B, Georgieva, E.I., Sendra, R., and Hansen, J.C. (1998) Gcn5p, a Transcription-Related Histone Acetyltransferase, Acetylates Nucleosomes and Folded Nucleosomal Arrays in the Absence of Other Protein Subunits. J. Biol. Chem. 273, 32388-32392. |
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NIH PubMed publications list for Jeffrey C. Hansen (This is a link to an external site.) |
Laboratory Web Page |
| http://hansenlab.bmb.colostate.edu/ |
Mailing Address: |
| Dept of Biochemistry and Molecular Biology 1870 |
| Colorado State University |
| Fort Collins, CO 80523-1870 |