Chris L. Woodcock

Photograph of First Last

Emeritus Professor

Gilbert Woodside Professor

Director, Central Microscopy Facility

Contact Info

Phone: 413-545-2825
Office: 364E Morrill IV South

Education

B.Sc. University College London, 1963
Ph.D., University College London, 1966

Postdoctoral

1966-1967 University of Chicago
1967-1969 Harvard University

Visiting Scientist

1986-1987 Max Plank Institute, Munich
1992-1993 University of Lausanne; Karolinska Institute, Stockholm

Research Interests

Nuclear Structure and Function

The cell nucleus is the site of a variety of highly organized activities including DNA replication, specific gene transcription, and mRNA processing and transport. Yet, when observed with the light or electron microscope, there is little indication of the structural organization required to support these activities. For several years, I have been investigating nuclear architecture with the aim of understanding the degree to which the apparent lack of structural order is real, and the degree to which it stems from our inability to preserve and image the very labile components. Investigation has involved the use and development of techniques for low temperature microscopy and 3-D reconstruction, in conjunction with more conventional biochemical and immunological methods. We find that these techniques provide a rather different view of the nuclear interior than found in textbooks. Chromatin fibers, for example, deviate to a large extent from an ordered array of nucleosomes, but the disorder can be explained by application of very simple construction rules. Results suggest that current concepts of structure of 'active' and 'inactive' chromatin need to be revised. Already, there is large and rapidly growing body of information about the molecular aspects of events occurring in the nucleus. It is my goal to provide a framework so that these events can be understood within the larger scale structure of the nucleus.

Representative Publications

Grigoryev, S.A., Woodcock, C.L. 2012. Chromatin organization - The 30nm fiber. Exp. Cell. Res., 318: 1448-55. Epub. 2012, Feb. 24. PMID: 22394510.

Panchenko, T., Sorensen, T.C., Woodcock, C.L., Kan, Z.Y., Wood, S., Resch, M.G., Luger, K., Englander, S.W., Hansen, J.C., Black, B.E. 2011 Replacement of histone H3 with CENP-A directs global nucleosome array condensation and loosening of nucleosome superhelical termini. Proc. Natl. Acad. Sci. USA, 108: 16588-93. Epub. 2011, Sep. 26. PMID: 21949362.

Hansen, J.C., Ghosh, R.P., Woodcock, C.L. 2010. Binding of the Rett syndrome protein, MeCP2, to methylated and unmethylated DNA and chromatin. IUBMB Life, 62: 732-8. Review. PMID: 21031501.

Ghosh, R.P., Horowitz-Scherer, R.A., Nikitina, T., Shlyakhtenko, L.S., Woodcock, C.L. 2010. MeCP2 binds cooperatively to its substrate and competes with histone H1 for chromatin binding sites. Mol. Cell. Biol., 30: 4656-70. PMID: 20679481.

Woodcock, C.L., Ghosh, R.P. 2010. Chromatin Higher-order Structure and Dynamics. Cold Spring Harb. Perspect. Biol., 2(5): a000596. Epub. 2010, Apr 7. PMID: 20452954.

Ghosh, R.P., Nikitina, T., Horowitz-Scherer, R.A., Gierasch, L.M., Uversky, V.N., Hite, K., Hansen, J.C., Woodcock, C.L. 2010. Unique Physical Properties and Interactions of the Domains of Methylated DNA Binding Protein 2. Biochemistry, Epub. Apr 28. PMID: 20405910.

Yan, Z., Delannoy, M., Ling, C., Daee, D., Osman, F., Muniandy, P.A., Shen, X., Oostra, A.B., Du, H., Steltenpool, J., Lin, T., Schuster, B., Décaillet, C., Stasiak, A., Stasiak, A.Z., Stone, S., Hoatlin, M.E., Schindler, D., Woodcock, C.L., Joenje, H., Sen, R., de Winter, J.P., Li, L., Seidman, M.M., Whitby, M.C., Myung, K., Constantinou, A., Wang, W. 2010. A histone-fold complex and FANCM form a conserved DNA-remodeling complex to maintain genome stability. Mol. Cell, 37(6): 865-78. PMID: 20347428.

Johnson, A., Li, G., Sikorski, T.W., Buratowski, S., Woodcock, C.L., Moazed, D. 2009 Reconstitution of heterochromatin-dependent transcriptional gene silencing. Mol. Cell, 35(6): 769-81. PMID: 19782027.

Grigoryev, S.A., Arya, G., Correll, S., Woodcock, C.L., Schlick, T. 2009. Evidence for heteromorphic chromatin fibers from analysis of nucleosome interactions. Proc Natl. Acad. Sci. U S A., 106(32): 13317-22. PMID: 19651606.

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(2): 276-88. PMID: 19099415.

Margueron, R., Li, G., Sarma, K., Blais, A., Zavadil, J., Woodcock, C.L., Dynlacht, B.D., Reinberg, D. 2008. Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms. Mol. Cell, 32: 503-18. PMID: 19026781.

Dechassa, M.L., Zhang, B., Horowitz-Scherer, R., Persinger, J., Woodcock, C.L., Peterson, C.L., Bartholomew, B. 2008. Architecture of the SWI/SNF-nucleosome complex. Mol. Cell Biol. , 2008 19: 6010-21. PMID: 18644858.

Ghosh, R.P., Horowitz-Scherer, R.A., Nikitina, T., Gierasch, L.M., Woodcock, C.L. 2008. Rett syndrome-causing mutations in human MeCP2 result in diverse structural changes that impact folding and DNA interactions. J. Biol. Chem., 283: 20523-34.

McBryant, S.J., Krause, C., Woodcock, C.L., 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.

Nikitina, T., Xi, S., Ghosh, R., Horowitz-Scherer, R.A., Hansen, J.C., Woodcock, C.L. 2007. Multiple modes of binding of the methylated DNA binding protein MeCP2 to chromatin. Mol. Cell Biol. 27: 864-877.

Adams, V.H., McBryant, S.J., Wade, P.A., Woodcock, C.L., Hansen, J.C. 2007. Intrinsic disorder and autonomous domain function in the multifunctional nuclear protein, MeCP2. J. Biol. Chem., 282: 15057-15064.

Nikitina, T., Ghosh, R..P, Horowitz-Scherer, R.A., Hansen, J.C., Grigoryev, S.A., Woodcock, C.L. 2007b. MeCP2-chromatin interactions include the formation of chromatosome-like structures and are altered in mutations causing Rett syndrome. J. Biol. Chem., 282: 28237-45.

Fan, Y., Skoultchi, A.I. and Woodcock, C.L. 2006. Role of histone H1 in chromatin structure and function: H1 stoichiometry and nucleosome repeat length. Chromosome Research, 14: 17-25.

Horowitz-Scherer, R.A., Woodcock, C.L. 2006. Organization of interphase chromatin. Chromosoma, Feb; 115(1): 1-14.

Woodcock, C.L. 2005. Chromatin architecture. Curr. Opin. Struct. Biol., 16: 1-8.

Fan, Y., Nikitina, T., Zhao, J., Fleury, T.J., Bhattacharyya, R., Bouhassira, E., Stein, A., Woodcock, C.L., and Skoultchi, A.I. 2005. Histone H1 depletion in mammals alters global chromatin structure but causes specific changes in gene regulation. Cell, 123(7): 1199-212

Francis, N.J., Kingston, R.E. and Woodcock, C.L. 2004. Chromatin compaction by a Polycomb group protein complex. Science, 306: 1574-1577.

Grigoryev, S.A., Nikitina, T., Pehrson, J., Singh, P., Woodcock, C.L. 2004. Dynamic relocation of epigenetic chromatin markers reveals a dynamic role of constitutive heterochromatin in the transition from proliferation to quiescence. J. Cell Sci., 117: 6153-6062.

Horowitz-Scherer, R.A. and Woodcock, C.L. 2004. Electron Microscopy of chromatin and chromatin remodeling complexes. Meth. Enzymol., 376: 29-47.

Nikitina, T. and Woodcock, C.L. 2004. Closed chromatin loops at the ends of chromosomes. J. Cell Biol., 166: 161-165.

Smith, C.L., Horowitz-Scherer, R., Flanagan, J.F., Woodcock, C.L., Peterson, C.L. 2003 Structural analysis of the yeast SWI/SNF chromatin remodeling complex. Nat. Struct. Biol., 10: 141-5.

Georgel, P.T., Horowitz-Scherer, R.A., Adkins, N., Woodcock, C.L., Wade, P.A., 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: 32181-8.

Fan, Y., Nikitina, T., Morin-Kensicki, E.M., Zhao, J., Magnuson, T.R., Woodcock, C.L., Skoultchi, A.I. 2003. H1 linker histones are essential for mouse development and affect nucleosome spacing in vivo. Mol. Cell Biol., 2003, 23: 4559-72.

Springhetti, E.M., Istomina, N.E., Whisstock, J.C., Nikitina, T., Woodcock, C.L., Grigoryev, S.A. 2003. Folding and bridging of nucleosome arrays by MENT: the role of the M-loop and the RCL domains. J. Biol. Chem., 278: 43384-43393.

Woodcock, C.L. and Dimitrov, S. 2001. Higher order structure of chromatin and chromosomes. Curr. Opin. Gen. Dev., 11: 130-135.

Bednar, J., Studitsky, V.M., Grigoryev, S.A., Felsenfeld, G., and Woodcock, C.L. 1999. The nature of the nucleosomal barrier to transcription: direct observation of paused intermediates by electron cryomicroscopy. Mol. Cell, 4: 377-385.

Grigoryev, S.A., Bednar, J., and Woodcock, C.L. 1999. MENT, a heterochromatin protein that mediates higher order chromatin folding, is a new serpin family member. J. Biol. Chem., 274: 5626-5636.

Bednar, J., Horowitz, R.A., Grigoryev, S.A., Carruthers, L.M., Hansen, J.C., Koster, A.J., and Woodcock, C.L. 1998. Nucleosomes, linder DNA, and linker histone form a unique structural motif that directs the higher-order folding and compaction of chromatin. Proc. Natl. Acad. Sci., 95: 14173-14178.

Grigoryev, S.A. and Woodcock, C.L. 1998. Chromatin structure in granulocytes. A link between tight compaction and accumulation of a heterochromatin-associated protein (MENT). J. Biol. Chem., 273: 3082-3089.

Shim, E.Y., Woodcock, C., and Zaret, K.S. 1998. Nucleosome positioning by the winged helix transcription factor HNF3. Genes Dev., 12: 5-10.

Woodcock, C.L. and Horowitz, R.A. 1998. Electron microscopic imaging of chromatin with nucleosome resolution. Methods Cell Biol., 53: 167-186.

Woodcock, C.L. and Horowitz, R.A. 1998. Electron microscopy of chromatin. Methods, 12: 84-95.

Horowitz, R.A., Koster, A.J., Walz, J., and Woodcock, C.L. 1997. Automated electron microscope tomography of frozen-hydrated chromatin: the irregular three-dimensional zigzag architecture persists in compact, isolated fibers. J. Struct. Biol., 120: 353-362.

McPherson, C.E., Horowitz, R., Woodcock, C.L., Jiang, C., and Zaret, K.S. 1996. Nucleosome positioning properties of the albumin transcriptional enhancer. Nucleic Acids Res., 24: 397-404.

Bednar, J., Horowitz, R.A., Dubochet, J., and Woodcock, C.L. 1995. Chromatin conformation and salt-induced compaction: three dimensional structural information from cryoelectron microscopy. J. Cell Biol., 131: 1365-1376.