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Andrew J. Andrews, PhD
About
Education, Training & Credentials
Educational Background
- PhD, Biological Chemistry, University of Michigan, Ann Arbor, MI, 2006
- BS/MS Microbiology, NCSU, Raleigh, NC, 2000
Research Profile
Research Program
Research Interests
- Histone chaperone mediated acetylation (Rtt109-Vps75)
- Specificity and selectivity of p300 and CBP KATs
- How acetyl-CoA concentration can alter selectivity of histone acetylation
- How chromatin dynamics influence histone acetylation
Lab Overview
DNA is highly compacted to fit into cells. The initial compaction forms the nucleosome, with each nucleosome consisting of two copies of four histone proteins H2A, H2B, H3 and H4. A major mechanism regulating the accessibility of DNA for the purposes of transcription, replication, DNA recombination, and DNA repair is through post-translational modification (PTM, or chemical modification) of histones. The most common PTMs are acetylation and methylation, with multiple residues targeted on each of the histones. Specific PTMs and their location are associated with either activated or repressed states of chromatin. Changes in histone acetylation correlate with changes in disease. The importance of maintaining proper histone post-translational modifications is made clear by the numerous diseases that correlate with misregulation of these modifications: cancer, heart disease, fetal alcohol syndrome, and Alzheimer’s, to name a few. Specifically, these diseases have each been shown to lack adequate levels of histone acetylation at specific locations. In order to maintain the proper level of acetylation in a healthy cell, lysine acetyltransferases (KATs) are responsible for targeting specific lysines in the histone. Despite the importance of this biological activity, relatively little is known about the factors that influence the location and extent of these post-translational modifications. Understanding how histone acetylation is regulated and, importantly, how it can be manipulated by the environment or through the use of pharmacological agents would allow us to tailor treatments to reverse or even prevent those diseases associated with loss of specific histone acetylation.
People
Publications
Selected Publications
Kuo, Y.M., Henry, R.A., Huang, L., Chen, X., Stargell, L.A., Andrews, A.J. Utilizing targeted mass spectrometry to demonstrate Asf1-dependent increases in residue specificity for Rtt109-Vps75 mediated histone acetylation. PLoS One 10(3), 2015 PubMed
Henry, R.A., Kuo, Y.M., Bhattacharjee, V., Yen, T.J., Andrews, A.J. Changing the selectivity of p300 by acetyl-CoA modulation of histone acetylation. ACS Chem. Biol. 10(1): 146-156, 2015 PubMed
Kuo, Y.M., Henry, R.A., Andrews, A.J. A quantitative multiplexed mass spectrometry assay for studying the kinetic of residue-specific histone acetylation. Methods. 70(2-3), 127-133, 2014. PubMed
Haery, L., Lugo-Picó, J.G., Henry, R.A., Andrews, A.J., Gilmore, T.D. Histone acetyltransferase-deficient p300 mutants in diffuse large B cell lymphoma have altered transcriptional regulatory activities and are required for optimal cell growth. Mol. Cancer 13:29, 2014. PMC3930761 PubMed
Kuo, Y.M., Andrews, A.J. Correction: Quantitating the specificity and selectivity of Gcn5-mediated acetylation of histone H3. PLoS One. 8(10), 2013. PMC3806868 PubMed
Henry, R.A., Kuo, Y.M., Andrews, A.J. Differences in specificity and selectivity between CBP and p300 acetylation of histone H3 and H3/H4. Biochemistry 52(34):5746-59, 2013. PMC3756530 PubMed
Kuo, Y.M., Andrews, A.J. Quantitating the specificity and selectivity of Gcn5-mediated acetylation of histone H3. PLoS One 8:e54896, 2013. PMC3578832 PubMed
Andrews, A.J., Luger, K. Nucleosome structure(s) and stability: Variations on a theme. Annu. Rev. Biophys. 40:99-117, 2011. Review 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. PMC3082900 PubMed
Andrews, A.J., Chen, X., Zevin, A., Stargell, L.A., Luger, K. The histone chaperone Nap1 promotes nucleosome assembly by eliminating nonnucleosomal histone DNA interactions. Mol. Cell 37:834-842, 2010. PMC2880918 PubMed
Koutmou, K.S., Casiano-Negroni, A., Getz, M.M., Pazicni, S., Andrews, A.J., Penner-Hahn, J.E., Al-Hashimi, H.M., Fierke, C.A. NMR and XAS reveal an inner-sphere metal binding site in the P4 helix of the metallo-ribozyme ribonuclease P. Proc. Natl. Acad. Sci. USA 107:2479-2484, 2010. PMC2823894 PubMed
Geiss, B.J., Thompson, A.A., Andrews, A., Sons, R.L., Gari, H.H., Keenan, S.M., Peersen, O.B. Analysis of flavivirus NS5 methyltransferase cap binding. J. Mol. Biol. 385(5):1643-1654, 2009. PMC2680092 PubMed
Andrews, A., Downing, G., Brown, K., Park Y., Luger, K. A thermodynamic model for Nap1-histone interactions. J. Biol. Chem. 283(47):32412-32418, 2008. PMC2583301 PubMed
