Sean Taverna
855 N. Wolfe Street
Rangos 575
Baltimore MD 21205
Eukaryotic cells package their genomes in the form of chromatin, which is comprised of histone proteins and DNA. Modification of chromatin by chemical marks such as methylation and acetylation affects how cellular machineries interpret the genome. The Taverna laboratory studies how histone marks contribute to an “epigenetic/histone code” that may dictate chromatin-templated functions like transcriptional activation and gene silencing, as well as how these On/Off states are inherited/ propagated. For example, transcription-modulating protein complexes with PHD finger motifs (methyl lysine “readers”) or Bromodomains (acetyl lysine “readers”) often have enzymatic activities that “write” these same histone marks. To explore these connections we use biochemistry and cell biology in a variety of model organisms ranging from mammals to yeast and ciliates. The lab also investigates links between small RNAs and histone marks involved in gene silencing. Importantly, many histone binding proteins have clear links to human disease, notably melanoma, leukemia, and other cancers. By understanding the molecular links between epigenetic regulators and disease, we hope to identify new therapeutic targets and optimize pharmacological interventions.
Stephens, K.E., Zhou, W., Ji, Z., He, S., Ji, H., Guan, Y., Taverna, S.D. Sex differences in gene regulation in the dorsal root ganglion after nerve injury. BMC Genomics 20(1):147, 2019. Pub Med Reference
West, K.L., Byrum, S.D., Mackintosh, S.G., Edmonson, R.D., Taverna, S.D., Tackett, A.J. Proteomic Characterization of the Arsenic Response Locus in S. cerevisiae. Epigenetics 14(2):130-145, 2019. Pub Med Reference
Su, Z., Wang, F., Lee, J.H., Stephens, K.E., Papazyan, R., Voronina, E., Krautkramer, K.A., Thorpe, J.J., Boersma, M.D., Kuznetsov, V., Miller, M.D., Taverna, S.D., Phillips, Jr., G.N., Denu, J.M. Reader Domain Specificity and Lysine Demethylase-4 Family Function. Nat. Commun. 7:13387, 2016. Pub Med Reference
Gilbert, T.M., McDaniel, S.L., Byrum, S.D., Cades, J.A., Dancy, B.C.R., Wade, H., Tackett, A.J., Strahl, B.D., Taverna, S.D. An H3K36me3 binding PWWP protein targets the NuA3 acetyltransferase complex to coordinate transcriptional elongation at coding regions. Molecular and Cellular Proteomics 13(11):2883-2895, 2014. Pub Med Reference
Papazyan, R., Voronina, E., Chapman, J.R., Luperchio, T.R., Gilbert, T.M., Meier, E., Mackintosh, S.G., Shabanowitz, J., Tackett, A.J., Reddy, K.L., Coyne, R.S., Hunt, D.F., Liu, Y., Taverna, S.D. Methylation of histone H3K23 blocks DNA damage in pericentric heterochromatin during meiosis. eLife 3:e02996, 2014. Pub Med Reference
Cieniewicz, A.M., Moreland, L., Ringel, A.E., Mackintosh, S.G., Raman, A., Gilbert, T.M., Wolberger, C., Tackett, A.J., Taverna, S.D. The bromodomain of Gcn5 regulates site-specificity of lysine acetylation on histone H3. Molecular and Cellular Proteomics 13(11):2896-2910, 2014. Pub Med Reference
Yan, G., Eller, M.S., Elm, C., Larocca, C.A., Ryu, B., Panova, I.P., Dancy, B.M., Bowers, E.M., Meyers, D., Lareau, L., Cole, P.A., Taverna, S.D., Alani, R.M. Selective Inhibition of p300 HAT Blocks Cell Cycle Progression, Induces Cellular Senescence, and Inhibits the DNA Damage Response in Melanoma Cells. J Invest Dermatol. 133(10): 2444-2452, 2013. Pub Med Reference
Taverna SD, Cole PA. Drug discovery: Reader’s block. Nature. 468(7327):1050-1, 2010.
Taverna SD, Li H, Ruthenburg AJ, Allis CD and Patel DJ. How chromatin binding modules interpret histone modifications. Nat. Struct. Mol. Bio. 14:1025-1040, 2007.
Taverna SD, Ilin S, Rogers RS, Tanny JC, Lavender H, Li H, Baker L, Boyle J, Blair LP, Chait BT, Patel DJ, Aitchison JD, Tackett AJ, and Allis .D. Yng1 PHD finger binding to histone H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs. Molecular Cell. 24:785-796, 2006.
Taverna S.D., Coyne RS, and Allis CD. Methylation of histone H3 at lysine 9 targets programmed DNA elimination in Tetrahymena. Cell 110:701-711, 2002.