David T. Auble

Education

  • AB, Bowdoin College
  • PhD, Case Western Reserve University
  • Postdoc, Fred Hutchinson Cancer Research Center

Primary Appointment

  • Professor, Biochemistry and Molecular Genetics

Contact

Research Interest(s)

Molecular Mechanisms of Transcriptional Regulation

Research Description

We are interested in understanding how gene expression is regulated. Our main research goal is to understand the molecular mechanisms responsible for assembly and disassembly of transcription preinitiation complexes at promoters, a major regulatory step in the complex process of RNA synthesis. Much of our work exploits the budding yeast system, although we also work with human cells as well.

Our analysis of transcription preinitiation complex assembly led us to consider fundamental questions about chromatin binding dynamics in cells. We seek to understand not only pathways for assembly and activity of transcription complexes in vivo, but the time scales on which these processes occur, how efficient they are in a cell population, and how stable complexes are once they assemble on chromatin. To address these questions, we developed a method that allows us to measure chromatin binding kinetics at specific chromosomal sites in cells. We also have a longstanding interest in the molecular mechanisms of regulatory factors that control transcription complex assembly, which we address using combined biochemical, biophysical, molecular, genetic and genomic experimental approaches.

Selected Publications

  • Chen X, Poorey K, Carver M, Müller U, Bekiranov S, Auble D, Brow D. Transcriptomes of six mutants in the Sen1 pathway reveal combinatorial control of transcription termination across the Saccharomyces cerevisiae genome. PLoS genetics. 2017;13(6): e1006863. PMID: 28665995 | PMCID: PMC5513554
  • Zaidi H, Auble D, Bekiranov S. RNA synthesis is associated with multiple TBP-chromatin binding events. Scientific reports. 2017;7 39631. PMID: 28051102 | PMCID: PMC5209698
  • Zaidi H, Hoffman E, Shetty S, Bekiranov S, Auble D. Second-generation method for analysis of chromatin binding with formaldehyde crosslinking kinetics. The Journal of biological chemistry. 2017. PMID: 28972159
  • True J, Muldoon J, Carver M, Poorey K, Shetty S, Bekiranov S, Auble D. The Modifier of Transcription 1 (Mot1) ATPase and Spt16 Histone Chaperone Co-regulate Transcription through Preinitiation Complex Assembly and Nucleosome Organization. The Journal of biological chemistry. 2016;291(29): 15307-19. PMID: 27226635 | PMCID: PMC4946942
  • Viswanathan R, True J, Auble D. Molecular Mechanism of Mot1, a TATA-binding Protein (TBP)-DNA Dissociating Enzyme. The Journal of biological chemistry. 2016;291(30): 15714-26. PMID: 27255709 | PMCID: PMC4957054
  • Butryn A, Schuller J, Stoehr G, Runge-Wollmann P, Förster F, Auble D, Hopfner K. Structural basis for recognition and remodeling of the TBP:DNA:NC2 complex by Mot1. eLife. 2015;4. PMID: 26258880 | PMCID: PMC4565979
  • Hoffman E, Frey B, Smith L, Auble D. Formaldehyde crosslinking: a tool for the study of chromatin complexes. The Journal of biological chemistry. 2015;290(44): 26404-11. PMID: 26354429 | PMCID: PMC4646298
  • Hoffman E, Frey B, Smith L, Auble D. Formaldehyde crosslinking: a tool for the study of chromatin complexes. The Journal of biological chemistry. 2015;290(44): 26404-11. PMID: 26354429 | PMCID: PMC4646298
  • Poorey K, Viswanathan R, Carver M, Karpova T, Cirimotich S, McNally J, Bekiranov S, Auble D. Measuring chromatin interaction dynamics on the second time scale at single-copy genes. Science (New York, N.Y.). 2013;342(6156): 369-72. PMID: 24091704 | PMCID: PMC3997053
  • Moyle-Heyrman G, Viswanathan R, Widom J, Auble D. Two-step mechanism for modifier of transcription 1 (Mot1) enzyme-catalyzed displacement of TATA-binding protein (TBP) from DNA. The Journal of biological chemistry. 2012;287(12): 9002-12. PMID: 22298788 | PMCID: PMC3308732
  • Snf2/Swi2 ATPase structure and function. Biochimica et biophysica acta. 2011;1809(9): 469. PMID: 21907167
  • Hyland E, Molina H, Poorey K, Jie C, Xie Z, Dai J, Qian J, Bekiranov S, Auble D, Pandey A, Boeke J. An evolutionarily 'young' lysine residue in histone H3 attenuates transcriptional output in Saccharomyces cerevisiae. Genes & development. 2011;25(12): 1306-19. PMID: 21685365 | PMCID: PMC3127431
  • Viswanathan R, Auble D. One small step for Mot1; one giant leap for other Swi2/Snf2 enzymes? Biochimica et biophysica acta. 2011;1809(9): 488-96. PMID: 21658482 | PMCID: PMC3171519
  • Wade S, Auble D. The Rad23 ubiquitin receptor, the proteasome and functional specificity in transcriptional control. Transcription. 2011;1(1): 22-6. PMID: 21327160 | PMCID: PMC3035185
  • Wollmann P, Cui S, Viswanathan R, Berninghausen O, Wells M, Moldt M, Witte G, Butryn A, Wendler P, Beckmann R, Auble D, Hopfner K. Structure and mechanism of the Swi2/Snf2 remodeller Mot1 in complex with its substrate TBP. Nature. 2011;475(7356): 403-7. PMID: 21734658 | PMCID: PMC3276066
  • Poorey K, Sprouse R, Wells M, Viswanathan R, Bekiranov S, Auble D. RNA synthesis precision is regulated by preinitiation complex turnover. Genome research. 2010;20(12): 1679-88. PMID: 20855454 | PMCID: PMC2989994
  • Wade S, Poorey K, Bekiranov S, Auble D. The Snf1 kinase and proteasome-associated Rad23 regulate UV-responsive gene expression. The EMBO journal. 2009;28(19): 2919-31. PMID: 19680226 | PMCID: PMC2760106
  • The dynamic personality of TATA-binding protein. Trends in biochemical sciences. 2008;34(2): 49-52. PMID: 19038550 | PMCID: PMC2933749
  • Basu D, Walkiewicz M, Frieman M, Baric R, Auble D, Engel D. Novel influenza virus NS1 antagonists block replication and restore innate immune function. Journal of virology. 2008;83(4): 1881-91. PMID: 19052087 | PMCID: PMC2643796
  • Sprouse R, Karpova T, Mueller F, Dasgupta A, McNally J, Auble D. Regulation of TATA-binding protein dynamics in living yeast cells. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(36): 13304-8. PMID: 18765812 | PMCID: PMC2533185
  • Sprouse R, Shcherbakova I, Cheng H, Jamison E, Brenowitz M, Auble D. Function and structural organization of Mot1 bound to a natural target promoter. The Journal of biological chemistry. 2008;283(36): 24935-48. PMID: 18606810 | PMCID: PMC2529012
  • Sprouse R, Wells M, Auble D. TATA-binding protein variants that bypass the requirement for Mot1 in vivo. The Journal of biological chemistry. 2008;284(7): 4525-35. PMID: 19098311 | PMCID: PMC2640957
  • Dasgupta A, Sprouse R, French S, Aprikian P, Hontz R, Juedes S, Smith J, Beyer A, Auble D. Regulation of rRNA synthesis by TATA-binding protein-associated factor Mot1. Molecular and cellular biology. 2007;27(8): 2886-96. PMID: 17296733 | PMCID: PMC1899949
  • Sprouse R, Brenowitz M, Auble D. Snf2/Swi2-related ATPase Mot1 drives displacement of TATA-binding protein by gripping DNA. The EMBO journal. 2006;25(7): 1492-504. PMID: 16541100 | PMCID: PMC1440317