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Home > Faculty
& Staff > Jeffrey Fillingham |
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Jeffrey
Fillingham
Assistant
Professor
B.Sc.H., University of Toronto
Ph.D., York University
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Courses
Offered:
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BLG307
(Molecular Biology) and BLG144 (Biology II) in 2009-2010.
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Teaching
Interests:
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The
nucleosome consists of a short stretch (147bp) of DNA wrapped
within a histone octamer composed of heterodimers of core histones
H2A with H2B, and H3 with H4. 'Chromatin' refers to genomic DNA
packaged within a series of repeating nucleosomes. In eukaryotic
cells changes in chromatin structure regulate nuclear processes
such as transcription, DNA repair and DNA replication. One method
used by the cell to regulate chromatin structure occurs at the
nucleosomal level i.e. by the post-translational modification
and remodelling of histones already assembled onto DNA. Chromatin
structure may also be regulated during the process of assembling
histones onto DNA, or chromatin assembly. Chromatin assembly occurs
during DNA replication (replication-coupled) and other times in
the cell cycle (replication-independent). Histone chaperones are
proteins that coordinate chromatin assembly.
My long-term research goal is to provide a molecular understanding
of how chromatin assembly influences nuclear events, and to define
the role in this process of PTMs such as histone acetylation.
I utilize as a model system baker's yeast Saccharmyces cerevisiae
to explore how histone chaperones interact with histone modifying
enzymes to regulate chromatin assembly and how this affects nuclear
processes such as gene expression. In addition, I exploit the
unique biology of the ciliated protozoan Tetrahymena thermophila
to discover novel roles for histone chaperones, their associated
histone modifying activities, and chromatin assembly. Through
the use of unicellular model systems, I hope to understand by
analogy how defects in chromatin assembly can contribute to disease
progression in humans, such as the transformation process where
cells become cancerous.
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Selected
Publications:
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*
Fillingham, J., *Kainth, P., Lambert, J.P., Van Bakel, H.,
Tsui, K., Nislow, C., Hughes, T., Figeys, D., Greenblatt, J.,
and B.J. Andrews. In Press, Molecular Cell.
A two-color cell array screen reveals interdependent roles for
histone chaperones and a chromatin boundary regulator in histone
gene repression. * Equal contribution
Fillingham
J., and J.F. Greenblatt. 2008. A histone code for chromatin
assembly. Cell. 34(2):206-8.
Fillingham,
J., Recht, J., Silva, A., Suter, B., Emili, A., Stagljar,
I., Krogan, N.J., Allis, C.D., Keogh, M.C., and J.F. Greenblatt.
2008. Chaperone Control of the Activity and Specificity of the
H3 Acetyltransferase Rtt109. Mol Cell Biol. 28(13):4342-53.
Collins,
S.R., Miller, K.M., Maas, N.L., Roguev, A., Fillingham, J.,
Chu, C.S., Schuldiner, M., Gebbia, M., Recht, J., Shales, M.,
Ding, H., Xu, H., Han, J., Ingvarsdottir, K., Cheng, B., Andrews,
B., Berger S.L., Heiter, P., Zhang, Z., Brown, G.W., Ingles, C.J.,
Boone, C., Emili, A., Allis, C.D., Toczyski, D., Weissman, J.,
Greenblatt, J.F., and N.J. Krogan. 2007. Genetic interactions
reveal the functional relationships within and between protein
complexes. Nature 446:806-10.
Fillingham,
J., Keogh, M.C., and N.J. Krogan. 2006. H2AX and its role
in DNA Double-Strand Break Repair. Biochemistry and Cellular Biology
84:568-77.
*Keogh,
M.C., *Kim, J.A., *Downey, M., Fillingham, J., Chowdhury,
D., Harrison, J.C., Onishi, M., Datta, N., Galicia, S., Emili,
A., Lieberman, J., Shen, X., Buratowski, S., Haber, J.E., Durocher,
D., Greenblatt, J.F., and N.J. Krogan. 2005. A phosphatase complex
that dephosphorylates H2AX regulates DNA damage checkpoint recovery.
Nature: 439:497-501.
*Krogan,
N.J., *Lam, M.H., *Fillingham, J., *Keogh, M.C., Gebbia,
M., Li, J., Datta, N., Cagney, G., Buratowski, S., Emili, A.,
and J.F. Greenblatt. 2004. Proteasome involvement in the repair
of DNA double-strand breaks. Molecular Cell 22:1027-34. * Equal
contribution
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