Biochemistry and Molecular Biology
Penn State Science
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Frank Pugh

Frank Pugh

Main Content

  • Evan Pugh Professor
  • Willaman Chair in Molecular Biology and
  • Professor of Biochemistry and Molecular Biology
456A North Frear Laboratory
University Park, PA 16802
Email: bfp2@psu.edu
Phone: (814) 863-8252

Research Interests

34th Summer Symposium in Molecular BiologyBiochemistry and genomics and eukaryotic transcription regulation

Graduate Programs

BG, BMMBMCIBS

Research Summary

Transcription regulation mechanisms across eukaryotic genomes

Research in the Pugh laboratory is devoted to understanding how genes are controlled in eukaryotic cells. Since the transcription machinery is fundamentally the same in all eukaryotes, most experiments are conducted on yeast, as they allow for the most efficient means of discovering transcriptional regulatory mechanisms.  Lessons learned from this model organism provide a foundation for conducting similar experiments in human cells. This approach helps us understand how genes are regulated in humans, and how mis-regulation of genes leads to diseases such as cancer.

The eukaryotic transcription machinery and its surrounding chromatin mileux consist of hundreds of distinct proteins, each having a specific function.  DNA sequence-specific regulators read the transcriptional regulatory code in the DNA by binding to promoter elements and orchestrating the assembly and disassembly of the transcription machinery.  This entire process takes place in the context of chromatin, whose fundamental building block is the nucleosome. The structure, composition, and placement of nucleosome along the genome is highly regulated, and mis-regulated in cancers.

The Pugh lab utilizes biochemistry, molecular biology, and genomics to understand gene regulatory mechanisms and how they are integrated into the global gene regulatory network.  The lab developed ChIP-seq technology and a derivative called ChIP-exo that maps the genomic binding locations of proteins at near base-pair resolution. These techniques provide greater detail and insight into how proteins bind to their target sites in living cells. The genomic mapping technology involves the collection of billions of data points, that report on the plasticity of the transcription machinery and its regulators across the genome.  Computational data analysis is used to integrate biochemically-defined regulatory mechanisms with the goal of generating a unified and mechanistically-defined gene regulatory network.

 

Selected Publications

  • Rhee, H-S., Bataille, A. R., Zhang, L., and Pugh, B.F. (2014) Subnucleosomal Structures and Nucleosome Asymmetry Across a Genome. Cell 159, 1377-1388. PMID: 25480300

  • Chang GS, Chen XA, Park B, Rhee HS, Li P, Han KH, Mishra T, Chan-Salis KY, Li Y, Hardison RC, Wang Y, Pugh BF. (2014) A comprehensive and high-resolution genome-wide response of p53 to stress. Cell Rep. 8, 514-27. PMID: 25043190

  • Yen, K., Vinayachandran, V., and Pugh, B.F. (2013). Genome-wide structural integration of SWR-C and INO80 chromatin remodelers at +1 nucleosomes. Cell 154, 1246-1256. PMID: 24034248

  • Yen, K., Vinayachandran, V., Batta, K., Koerber, R.T., and Pugh, B.F. (2012). Genome¬≠wide nucleosome specificity and directionality of chromatin remodelers. Cell. 149, 1461-1473. PMID: 22726434.

  • Chang, G. S., Noegel, A. A., Mavrich, T. N., Muller, R., Tomsho, L., Ward, E., Felder, M., Jiang, C., Eichinger, L., Glockner, G., Schuster, S. C. & Pugh, B. F. (2012). Unusual combinatorial involvement of poly-A/T tracts in organizing genes and chromatin in Dictyostelium. Genome Res. 22, 1098-1106. PMID: 22434426

  • Rhee, H-S., and Pugh, B.F. (2012) Genome-wide structure and organization of eukaryotic pre-initiation complexes. Nature, AOP Jan. 18.
  • Batta, K., Zhang, Z., Yen, K., Goffman, D. B., and Pugh, B.F. (2011) Genome-wide function of H2B ubiquitylation in promoter and genic regions. Genes & Devel,  25:2254-65.
  • Rhee, H-S., and Pugh, B.F. (2011) Comprehensive genome-wide protein-DNA interactions detected at single nucleotide resolution. Cell, 147:1408-19.
  • Zhang, Z., Wippo, C.J., Wal, M. Ward, E., Korber, P., Pugh, B.F. (2011) A Packing Mechanism for Nucleosome Organization Reconstituted Across a Eukaryotic Genome. Science, 332:977-80.
  • Zhang, L., Ma, H., and Pugh, B.F. (2011). Stable and dynamic nucleosome states during a meiotic developmental process. Genome Res., 19, 360-371
  • Zhang, Z., and Pugh, B.F. (2011). High-resolution genome-wide mapping of the primary structure of chromatin. Cell 144, 175-186.
  • Venters, B.J., Wachi, S., Mavrich, T.N., Andersen, B.E., Jena, P., Sinnamon, A.J., Jain, P., Rolleri, N.S., Jiang, C., Hemeryck-Walsh, C., and Pugh, B.F.  (2011) A Comprehensive Genomic Binding Map of Gene and Chromatin Regulatory Proteins in Saccharomyces.  Mol Cell, 41, 480-492.
  • Ghosh, S., and Pugh, B.F. (2011) Sequential recruitment of SAGA and TFIID in a genomic response to DNA damage in Saccharomyces.  Mol Cell Biol, 31, 190-202.
  • Samorodnitsky, E., and Pugh, B.F. (2010) Genome-wide modeling of transcription preinitiation complex disassembly mechanisms using ChIP-chip data. PLoS Computational Biology 6:e1000733
  • Jiang, C., and Pugh, B.F. (2009). A compiled and systematic reference map of nucleosome positions across the Saccharomyces genome. Genome Biol. 10, R109.
  • Koerber, R.T., Rhee, H.S., Jiang, C., and Pugh, B.F. (2009). Interaction of transcriptional regulators with specific nucleosomes across the Saccharomyces genome. Mol Cell 35, 889-902.
  • Venters, B., and Pugh, B.F. (2009). How eukaryotic genes are transcribed. Crit. Rev. Bioch. Mol. Biol. 44, 117-1141.
  • Jiang, C., and Pugh, B.F. (2009).  Nucleosome positioning and gene regulation: advances through genomics.Nature Rev. Genet. 10, 161-172.
  • Venters, B., and Pugh, B.F. (2009). A canonical promoter organization of the transcription machinery and its regulators in the Saccharomyces genome. Genome Res.  19, 360-371.
  • Mavrich, T.N., Ioshikhes, I.P., Venters, B.J., Jiang, C., Albert, I., Tomsho, L.P., Qi, J., Schuster, S.C., and Pugh, B.F. (2008). A barrier nucleosome model for statistical positioning of nucleosomes throughout the yeast genome. Genome Res.  7, 1073-1083.
  • Mavrich, T.N., Jiang, C., Ioshikhes, I.P., Li, X., Venters, B.J., Zanton, S.J., Tomsho, L.P., Qi, J., Glaser, R., Schuster, S.C., Gilmour, D.S., Albert, I., and Pugh, B.F. (2008). Nucleosome organization in the Drosophila genome. Nature 453, 358-362. 
  • Huisinga, K.L. and Pugh, B.F. (2007) A TATA Binding Protein regulatory network that governs transcription complex assembly. Genome Biol 8(4): R46.
  • Albert, I., Mavrich, T. N., Tomsho, L. P, Qi, J., Zanton, S. J., Schuster, S. C., and Pugh, B.F. (2007) Translational and rotational settings of H2A.Z nucleosomes across the S. cerevisiae genome. Nature 446, 572-576.  
  • Ioshikhes, I., Albert, I., Zanton, S. J., and Pugh, B.F. (2006). Nucleosome positions predicted through comparative genomics. Nature Genetics. 38, 1210-1215.  Subject of commentary.