Dr. Andrew VanDemark

Genetics
K. Arndt
T.-L. Ashman
G. Campbell
D. Chapman
G. Hatfull
J. Hildebrand
L. Jacobson
S. Kalisz
J. Martens
V. Oke
W. Saunders
B. Stronach
S. Tonsor
R. Wood

Microbiology
G. Hatfull
R. Hendrix
J. Lawrence
V. Oke
J. Pipas
M. Popa
I. Campbell
R.L. Duda
S. Godfrey

Molecular Biology
K. Arndt
J. Franzen
P. Grabowski
G. Hatfull
R. Hendrix
L. Jen-Jacobson
J. Martens
C. Peebles
J. Pipas
J. Rosenberg
A. Schwacha
C. Walsh

Plant Biology
T.-L. Ashman
W. Carson
S. Kalisz
V. Oke
C. Partanen
S. Tonsor
B. Traw

Science Education
A. Bledsoe
K. Curto
L. Daniels
S. Godfrey
N. Kaufmann
C. LaFave
J. Newman
E. Polinko
M. Popa
L. Roberts
T. Seiflein
R. Sherwin
A. Slinskey Legg

Structural Biology
M. Grabe
J. Hempel
R. Hendrix
L. Jen-Jacobson
J. Rosenberg
A. VanDemark

Former Faculty

Photo of Dr.
VanDemark

Structural Biology of Chromatin

Assistant Professor

Dr. VanDemark received his Ph.D. in 2001 with Cynthia Wolberger at Johns Hopkins University, performed his postdoctoral research with Christopher Hill at the University of Utah, and joined the Department in 2007.

Currently, Dr. VanDemark is accepting graduate students in his laboratory. Dr. VanDemark is accepting undergraduate researchers, and does sponsor students in other laboratories.

Professional Interests - Publications - Contact Information - Lab Personnel

Professional Interests of Andrew VanDemark

The lab uses X-ray crystallography as well as a broad range of biochemical and biophysical techniques to investigate important aspects of chromatin biology including molecular recognition and regulation. In eukaryotes, DNA is packaged in the form of chromatin, with the basic repeating unit being the nucleosome which contains ~147bp of DNA wrapped around a histone octamer. Therefore, many essential processes located in the nucleus, including transcription, replication, and DNA repair require the functions of protein complexes that recognize and function in the context of chromatin.

Chromatin remodeling complexes are typically large multi-subunit protein complexes that use the energy of ATP hydrolysis to mobilize the position of nucleosomes. In additional to an ATPase motor subunit that drives remodeling, these complexes also contain various domains, including bromodomains, which recognize specific features of the histones. An important issue for chromatin remodeling complexes is how their bromodomains recognize particular acetylated lysine residues in histones. The Rsc4 subunit of the yeast remodeler RSC contains an essential tandem bromodomain (TBD) that binds acetylated histone H3K14. We have solved a series of crystal structures that reveal a compact TBD that binds H3K14ac in the second bromodomain and, unexpectedly, binds acetylated Rsc4 K25 in the first bromodomain. Rsc4 K25 acetylation inhibits binding to H3K14ac peptide and mutation of Rsc4 K25 results in altered growth rates. These data suggest an autoregulatory mechanism in which Gcn5 performs both the activating (H3K14) and inhibitory (Rsc4 K25) modifications, perhaps to provide temporal regulation.

In yeast, the FACT complex (Facilitates Chromatin Transcription) is a three subunit protein complex consisting of the Pob3-Spt16 dimer and the DNA binding protein Nhp6a. In contrast to chromatin remodelers, FACT is an ATP-independent chromatin reorganizer that functions to assist the passage of polymerases through nucleosomal locations on a chromatin template. We have solved the structure of the middle domain of Pob3 protein, which had no previously known structure and no apparent homologs. The results of our work revealed that the Pob3-M domain is a double PH domain. Genetic and biochemical results revealed a conserved patch on the surface of one of the PH domains, and that this patch plays an important role in DNA replication.

My current research efforts remain focused on the structural biology of proteins and protein complexes that interact with chromatin. Notably, we have begun work on histone chaperones, proteins that bind histones and function in chromatin assembly and thereby play a fundamental role in replication, transcription, and DNA repair. Also we are actively pursuing other proteins of interest, including viral integrases and proteins involved in the regulation of transcriptional elongation.

Publication Archive
12 Citations
10 Abstracts
10 PDFs

Recent Publications of Andrew VanDemark

Welch, B., A.P. VanDemark, A. Heroux, C.P. Hill, and M.S. Kay (2007) Potent D-peptide inhibitor of HIV-1 entry. Proc. Natl. Acad. Sci., USA :

VanDemark, A.P., M. Kasten, E. Ferris, A. Heroux, C.P. Hill, and B.R. Cairns (2007) Autoregulation of the Rsc4 Tandem Bromodomain by Gcn5 acetylation. Mol. Cell :In Press

VanDemark, A.P., M. Blanksma, E. Ferris, A. Heroux, C.P. Hill, and T. Formosa (2006) The structure of the yFACT Pob3-M domain, its interaction with the DNA replication factor RPA, and a potential role in nucleosome deposition. Mol. Cell 22:363-374 (PDF Reprint: 748 kb)

Macbeth, M.R., H.L. Schubert, A.P. Vandemark, A.T. Lingam, C.P. Hill, and B.L. Bass (2005) Inositol hexakisphosphate is bound in the ADAR2 core and required for RNA editing. Science 309:1534-1539 (PDF Reprint: 703 kb)

VanDemark, A.P., and C.P. Hill (2005) E1 on the move. Mol. Cell 17:474-475 (PDF Reprint: 93 kb)

VanDemark, A.P., and C.P. Hill (2004) Grabbing E2 by the tail. Nat. Struct. Mol. Biol. 11:908-909 (PDF Reprint: 316 kb)

VanDemark, A.P., and C.P. Hill (2003) Two-stepping with E1. Nat. Struct. Biol. 10:244-246 (PDF Reprint: 1000 kb)

VanDemark, A.P., and C.P. Hill (2002) Structural basis of ubiquitylation. Curr. Opin. Struct. Biol. 12:822-830 (PDF Reprint: 438 kb)

VanDemark, A.P., and C.P. Hill (2002) SUMO wrestling with specificity. Structure 10:281-282 (PDF Reprint: 69 kb)

VanDemark, A.P., R.M. Hofmann, C. Tsui, C.M. Pickart, and C. Wolberger (2001) Molecular insights into polyubiquitin chain assembly: crystal structure of the Mms2/Ubc13 heterodimer. Cell 105:711-720 (PDF Reprint: 482 kb)

Pickart, C.M., and A.P. VanDemark (2000) Opening doors into the proteasome. Nat. Struct. Biol. 7:999-1001 (PDF Reprint: 373 kb)

Jabet, C., E.R. Sprague, A.P. VanDemark, and C. Wolberger (2000) Characterization of the N-terminal domain of the yeast transcriptional repressor Tup1. Proposal for an association model of the repressor complex Tup1 x Ssn6. J. Biol. Chem. 275:9011-9018 (PDF Reprint: 295 kb)

How to Contact Andrew VanDemark

US Mail
University of Pittsburgh
Department of Biological Sciences
A518 Langley Hall
4249 Fifth Avenue
Pittsburgh, PA 15260

Phone, FAX, Internet
Office : (412) 648-0110
Lab : (412) 648-0111
FAX : (412) 624-4759
Email : andyv@pitt.edu
Web :

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