Andrew J. Andrews, PhD
Office Phone: 215-728-2762
Lab Phone: 215-728-2762
A cell contains two meters of DNA compacted 500,000-fold to fit in to the nucleus. Histones play a key role in compacting chromosomal DNA, which represents a major obstacle for proteins that need to access that DNA. One of the main ways that histone-DNA interactions are regulated is by chemical modification histones. The goal of my lab is to understand the link between the specificity of histone modifications and the impact of these modifications on chromatin dynamics, which directly affects gene expression. While the correlation between histone PTMs and disease is well established there are still critical gaps in our understanding of this relationship. The majority of histone modification enzymes can modify more than one location on a single histone, but little is known about how the location and extent of these modifications are regulated. Histone chaperones can interact with both histone modification enzymes and histones, and are proposed to aid the determinion which histone residues are modified. To determine how histone chaperones or other factors control which residue(s) on a histone become modified, my lab is pursuing two research aims:
- Determine the thermodynamic conditions which favor specific complexes between histones and histone-modifying enzymes;
- Develop experimental approaches that can monitor the post-translational modification of multiple residues as a function of time. A complimentary goal of my lab is to determine the impact of both single and multiple histone modifications on the thermodynamics of chromatin.
- Kuo, Y.M., Andrews, A.J. Quantitating the specificity and selectivity of Gcn5-mediated acetylation of histone H3. PLoS One 8:e54896, 2013. PubMed
- Böhm, V., Hieb, A.R., Andrews, A.J., Gansen, A., Rocker, A., Tóth, K., Luger, K., Langowski, J. Nucleosome accessibility governed by the dimer/tetramer interface. Nucleic Acids Res. 39(8):3093-3102, 2011. PubMed
- Andrews, A.J., Luger, K. Nucleosome structure(s) and stability: Variations on a theme. Annu. Rev. Biophys. 40:99-117, 2011. Review PubMed
- Andrews, A.J., Luger, K. A coupled equilibrium approach to study nucleosome thermodynamics. Methods Enzymol. 488:265-285, 2011. PMC – in process PubMed
- Andrews AJ, Chen X, Zevin A, Stargell LA, Luger K. The histone chaperone Nap1 promotes nucleosome assembly by eliminating nonnucleosomal histone DNA interactions. Mol Cell. 2010 Mar 26;37(6):834-42. PubMed
- Andrews, A.J., Luger, K. Histone Modiﬁcations, Chemistry and Structural Consequences of, Wiley Encyclopedia of Chemical Biology, DOI: 10.1002/9780470048672.wecb225, Epub, 15 May 2008.
- Park Y, Sudhoff K, Andrews A, Stargell L, Luger K. Histone chaperone specificity in Rtt109 activation. Nat Struct Mol Biol. 2008 Sep;15(9):957-64. 2. PubMed
- Andrews AJ, Downing G, Brown K, Park YJ, Luger K. A thermodynamic model for Nap1 - histone interactions. J Biol Chem. 2008 Nov 21;283(47):32412-8. Epub 2008 Aug 25. PubMed
- Geiss BJ, Thompson AA, Andrews AJ, Sons RL, Gari HH, Keenan SM, Peersen OB. Analysis of Flavivirus NS5 Methyltransferase Cap Binding. J Mol Biol. 2009 Feb 6;385(5):1643-54. Epub 2008 Dec 11. PubMed