Steven Hahn Curriculum Vitae

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1 Steven Hahn Curriculum Vitae CONTACT INFORMATION Fred Hutchinson Cancer Research Center 1100 Fairview Ave N. PO Box 19024, Mailstop A Seattle, WA Phone Laboratory Web site: CURRENT APPOINTMENTS Member, Division of Basic Sciences, Fred Hutchinson Cancer Research Center. July present Affiliate Professor, Department of Biochemistry, University of Washington School of Medicine. July present PREVIOUS APPOINTMENTS Investigator, Howard Hughes Medical Institute, July 1997-August 2005 Associate Member, Division of Basic Sciences, Fred Hutchinson Cancer Research Center. June 1992-June 1995 Affiliate Associate Professor, Department of Biochemistry, University of Washington School of Medicine. July 1996-July Assistant Member, Division of Basic Sciences, Fred Hutchinson Cancer Research Center. November May 1992 EDUCATION Post-doctoral Fellow in the laboratory of Dr. Leonard Guarente, September October Department of Biology, Massachusetts Institute of Technology, Cambridge, MA. Department of Biochemistry, Brandeis University, Waltham, MA. September September Ph.D. in Biochemistry, September Thesis Advisor: Dr. Robert Schleif. Thesis: Studies on Transcriptional Regulation of the Escherichia coli L-arabinose Operon. University of California, Santa Barbara, September, 1977 June B.A. (With High Honors), June 1979 Santa Rosa Jr. College, Santa Rosa, CA September 1975 June HONORS Investigator, Howard Hughes Medical Institute, July 1997-August 2005 Scholar Award, Leukemia and Lymphoma Society, June 1993 May 1998 Junior Faculty Award, American Cancer Society, January December 1993 Postdoctoral Fellowship, Damon Runyon-Walter Winchell Cancer Fund September September

2 SERVICE Board of Reviewing Editors, Science Magazine. July 2009-June 2014 Editorial Board, Molecular and Cellular Biology 2012-present Site visit team, National Cancer Institute, Laboratory of receptor biology and gene expression. May, Co-Organizer, Cold Spring Harbor Meeting on Mechanisms of Eukaryotic Transcription. August, 2007, 2009, Co-Organizer, FASEB meeting on Transcriptional Regulation During Cell growth, Differentiation, and Development. August NIH MGB Review Panel, September ; February 2015; November 2013 and June 2005 NIH CDF-1 Review Panel, February, 2002 NIH MBY Review Panel, February, 1996, 1994 GRANT SUPORT NIGMS RO1 GM Molecular Analysis of Eukaryotic Transcription 9/30/1995 to 5/31/2021. NIGMS RO1 GM Mechanisms of Eukaryotic Transcription Activation, 9/1/2005 to 6/30/2018 CONTRIBUTIONS TO SCIENCE 1. Discovery of DNA looping as a gene regulatory mechanism Regulation of transcription and other DNA-dependent processes by distantly located regulatory elements was a key problem in the 1980s-1990s. For example, transcription enhancers and related regulatory elements can be located thousands of base pairs distant from the start site of transcription. During my graduate work in Robert Schleif s laboratory, I defined a target for the bacterial regulatory protein arac located over 200 bp distant from the transcription start site. This contradicted earlier models that arac acts via binding near a cluster of protein binding sites adjacent to the promoter-bound RNA polymerase. My work, in combination with the work of two other graduate students and Robert Schlief, led to the discovery that arac works by DNA looping between one arac monomer bound to the distant repression site and another arac monomer bound adjacent to the RNA polymerase binding site. The resulting regulatory loop represses transcription until arabinose binds arac, breaking the loop, and allowing a reorganization of protein binding at the ara operon. This work was the first discovery of DNA looping as a gene regulatory mechanism and provided a breakthrough model for understanding the action of many elements and factors that act at over large distances. DNA looping is now a standard and well accepted mechanism for gene regulation in many different systems. a) Dunn, T., Hahn, S., Ogden, S., and Schleif, R. (1984) A Deletion Analysis of the 2

3 aracbad Regulatory Region: A Site -280 Base Pairs from the Start of Transcription that is Required for Repression. Proc. Natl. Acad. Sci. USA 81: PMID: b) Hahn, S., Dunn, T., and R. Schleif. (1984) Repression and CRP Stimulation of the arabad Promoter in vivo. J. Mol. Biol. 180: PMID: c) Hahn, S., Hendrickson, W., and R. Schleif. (1986) Transcription of Escherichia coli ara in vitro: The Cyclic AMP Receptor Protein Requirement for PBAD Induction that Depends on the Presence and Orientation of the arao2 site. J. Mol. Biol. 188: PMID: Defining and characterizing components and regulators of the basal transcription machinery In pioneering work during the 1980 s, Bob Roeder, Phil Sharp and Pierre Chambon s laboratories used chromatography of HeLa cell extracts to identify basal transcription factors. When combined, these crude fractions reconstituted accurately initiated Pol II transcription from TATA-containing promoters. The next key questions were: what are these factors and how do they function? Because of low abundance and tricky biochemical properties and, despite the efforts of many, none of these factors had been purified or the corresponding genes cloned in It was generally acknowledged that TATA binding protein (then termed TFIID) was the most critical component to isolate and characterize. While a postdoc in the Guarente lab, I teamed with Steve Buratowski in the Sharp lab to discover a yeast protein that could complement a HeLa transcription system lacking TBP. We went on to purify this factor and demonstrate that it was in fact TBP. Utilizing purified yeast TBP allowed us to determine the ordered assembly pathway for transcription preinitiation complex (PIC) assembly. After moving to my own laboratory at Fred Hutch, I cloned the gene encoding yeast TBP and began a long-term project to characterize this protein and other basal transcription factors. The identification and cloning of yeast TBP was a leap that allowed genetic and biochemical approaches for identifying genes encoding other basal factors. Examples of important factors my laboratory identified and cloned the corresponding genes include TFIIA, Mot1 (a TBP regulatory factor) Brf1 (a TFIIB-like Pol III factor) as well as the discovery that Rrn7 is a TFIIB-like Pol I factor and TFIIIB component Bdp1. Working with Ron Reeder s laboratory, we showed that TBP is used for transcription of all three nuclear RNA polymerases. Our combined work was a breakthrough in understanding the mechanisms of transcription and opened up many new avenues to approach the study of gene regulatory mechanisms that are today used by many laboratories. Four representative publications are given below: a) Buratowski, S., Hahn, S., Sharp, P.A., and L. Guarente (1988) Function of a yeast TATA element-binding protein in a mammalian transcription system. Nature 334: PMID: b) Hahn, S., Buratowski, S., Sharp, P.A., and L. Guarente (1989). Isolation of the gene 3

4 encoding the yeast TATA binding protein TFIID: a gene identical to the SPT15 suppressor of Ty element insertions. Cell 58: PMID: c) Colbert, T. and S. Hahn (1992). A yeast TFIIB related factor involved in RNA polymerase III transcription. Genes and Dev. 6: PMID: d) Knutson, B.A., and S. Hahn (2011). Yeast Rrn7 and human TAF1B are TFIIB-related RNA polymerase I general transcription factors. Science, 333: PMID: PMCID:PMC Determining the structure of TBP-DNA and TBP-TFIIA-DNA complexes. After the cloning of TBP, two other key questions were: (i) how does TBP bind DNA and nucleate the assembly of the preinitiation complex (PIC)? and (ii) could this structure lead to understanding the workings of the basal transcription machinery? After my cloning of the yeast TBP gene and expression of recombinant protein, I soon teamed up with James Geiger and Youngchang Kim in Paul Sigler s laboratory to determine the structure of TBP-DNA and TBP-DNA in complex with the basal factor TFIIA. My laboratory s role in this work included working out purification conditions for all proteins, generating and assaying many DNA and protein derivatives used in the crystallization work, analyzing the structure in the context of known biochemical and genetic properties, and biochemical and molecular experiments to follow up predictions of the structures. The two beautiful and complementary structures resulting from this work revealed the novel DNA binding mechanism of TBP and important clues about its role in nucleating assembly of the PIC. These structures have remained a rich resource for many genetic, biochemical and genomic studies carried out by numerous laboratories. a) Kim, Y., Geiger, J.H., Hahn, S. and Sigler, P.B. (1993). Crystal structure of a yeast TBP/TATA-box complex. Nature 365: PMID: b) Geiger, J.H., Hahn, S., Lee, S., Sigler, P.B. (1996). The crystal structure of the yeast TFIIA/TBP/DNA complex. Science, 272: PMID Mechanisms and architecture of the basal transcription machinery After the cloning and initial characterization of the basal factors by our own and other laboratories, the next important questions were: (i) how do these factors function together? (ii) how do the factors interface with gene regulatory factors?, and (iii) what is the structure of the complete PIC? This latter question is of great importance as answering this gives much insight into the function of the basal factors and the initiation mechanism as well as conserved features used by all cellular RNA polymerases. My laboratory s approach to these questions, over a period of 15+ years, has been to utilize a combination of biochemistry, molecular genetics, structural biology, and biophysics to get at the conserved fundamental mechanisms used in transcription. This work has revealed a number of novel mechanisms, many of which are conserved between all 4

5 three nuclear RNA polymerase systems. Examples of our work include defining the pathway of yeast PIC assembly, discovery of a transcription reinitiation intermediate termed the scaffold complex, and discovery of conserved mechanisms and factors utilized by all three nuclear RNA polymerases. We have also pioneered the use of chemical cleavage and crosslinking probes to determine the architecture of large protein complexes and first applied these techniques to the Pol II PIC. We initially mapped TFIIB binding on Pol II and, combining this information with known atomic structures, led to the first (correct) model for the structure of the PIC which has stood the test of time and led to years of ongoing research by many laboratories. We expanded this work to map the location of additional PIC components including TFIIF, TFIIE, and TFIIH. Mapping TFIIH was especially important as it led to a model for the action of the TFIIH subunit XPB/Ssl2, a DNA translocase, that is responsible for ATPdependent DNA opening during transcription initiation. In our collaboration with Jeff Ranish s laboratory (Institute for Systems Biol) we have also pioneered the use of protein crosslinking/mass spectrometry to delineate the architecture of large protein complexes including the basal factor TFIIH, the transcription coactivator (SAGA) and a Pol I basal factor termed core factor. We have recently extended our work to examine mechanisms used at TATA-less promoters using a combined biochemical and genomics approach. For example, in recent work we showed that TFIID binds and functions at nearly all Pol II promoters in contrast to earlier proposals. We have also teamed with biophysicist Eric Galburt s laboratory (Washington University) to utilize single molecule methods to dissect the dynamic mechanism of initiation and open complex formation to an unprecedented level of detail, which promises to be another breakthrough in the field. Four representative publications are given below: a) Chen H-T. and S. Hahn. (2004) Mapping the location of TFIIB within the RNA Polymerase II transcription preinitiation complex: A model for the structure of the PIC. Cell 119: PMID: b) Grünberg S., Warfield, L., and S. Hahn (2012) Architecture of the RNA polymerase II preinitiation complex and mechanism of ATP-dependent promoter opening. Nature Struct Mol Biol, 19: PMID: PMCID: PMC c) Fishburn, J., Tomko, E., Galburt, E. and S. Hahn S. (2015). Double stranded DNA translocase activity of transcription factor TFIIH and the mechanism of RNA Polymerase II Open Complex formation. Proc Natl Acad Sci USA, 112: PMID: PMCID:PMC d) Grünberg S, Henikoff S, Hahn S, Zentner GE. (2016). Mediator binding to UASs is broadly uncoupled from transcription and cooperative with TFIID recruitment to promoters. EMBOJ 35: Epub 2016 Oct 20. PMID:

6 5. Discovery of transcription activation mechanisms Since the discovery of the first Pol II transcription activators Gcn4 and Gal4, it has been recognized that understanding their mechanism is a fundamental problem in the gene regulation field. Pioneering work by Ptashne, Struhl and others led to the idea of activation by recruitment. However, over the past 20 years it has been unclear what factors are targeted by activators and how activators specifically bind their targets. In particular, the fact that most activators have different protein sequences and target multiple unrelated factors has been difficult to understand. Our work in this field began over 10 years ago when we used site-specific protein crosslinking of active transcription complexes to identify functional activator targets. We have continued this work using a combination of biochemistry, molecular genetics and structural biology in collaboration with Rachel Klevit s laboratory. Before our structural work, only a few activator-target structures were known and these were activators of a class that bound their target proteins tightly and specifically. In contrast, a large class of activators including Gal4, Gcn4, VP16, etc bind their targets with modest affinity and specificity. Our structural work on the Gcn4-Med15/Gal11 complex revealed the basis for this lack of specificity as the protein complex is fuzzy as Gcn4 can bind its target in Med15 in multiple orientations using purely hydrophobic contacts with low affinity and a short complex lifetime. This behavior potentially explains the mechanism of a large number of transcription activators. We are actively characterizing both natural and a very large number of synthetic activators to determine if this mechanism generally holds for many activators and to gain the ability to recognize functional activators from protein sequence alone. This ongoing work is in collaboration with Rachel Klevit (U. Washington) and Johannes Söding (Max Plank). Four representative publications are given below: a) Fishburn, J., Mohibullah, N., and S. Hahn (2005) Function of a eukaryotic transcription activation domain during the transcription cycle. Mol Cell 18: PMID: b) Herbig, E., Warfield, L., Fish, L., Fishburn, J., Knutson, B.A., Moorefield, B., Pacheco, D., and S. Hahn (2010). Mechanism of Mediator recruitment by tandem Gcn4 activation domains and three Gal11 activator-binding domains. Mol Cell Biol 30: PMID: PMCID: PMC c) Brzovic, P.S., Heikaus, C.C, Kisselev, L., Vernon, R., Herbig, E., Pacheco, D., Warfield, L., Littlefield, P., Baker, D., Klevit, R., and S. Hahn (2011). The acidic transcription activator Gcn4 binds the Mediator subunit Gal11/Med15 using a simple protein interface forming a fuzzy complex. Mol Cell, 44: PMID: PMCID: PMC d) Warfield, L., Tuttle, L.M., Pacheco, D., Klevit, R., and S. Hahn (2014). A sequencespecific transcription activator motif and powerful synthetic variants that bind Mediator using a fuzzy protein interface. Proc Natl Acad Sci USA Aug 26;111(34): E doi: /pnas Epub 2014 Aug 13. PMID: PMCID: PMC

7 PUBLICATIONS Tuttle LM, Pacheco D, Warfield L, Luo J, Ranish J, Hahn S, Klevit, R. Transcription activator-coactivator specificity is mediated by a large and dynamic fuzzy proteinprotein complex. biorxiv Nov 18;:1 44.DOI: (under review) Pacheco D, Warfield L, Brajcich M, Robbins H, Luo J, Ranish J, S. Hahn. Transcription activation domains of the yeast factors Met4 and Ino2: tandem activation domains with properties similar to the yeast Gcn4 activator. biorxiv. :1 38:DOI: (under review) Tomko, E., Fishburn, J., Hahn, S., and E. Galburt (2017) TFIIH generates a six base-pair open complex during RNAP II transcription initiation and start-site scanning. Nat Struct Mol Biol, 24: PMID: Warfield, L, Ramachandran, S, Baptista, T., Devys, D., Tora, L. and S. Hahn (2017). Transcription of Nearly All Yeast RNA Polymerase II-Transcribed Genes Is Dependent on Transcription Factor TFIID. Mol Cell, 68: PMID: Baptista, T, Grünberg, S, Minoungou, N., Koster, MJE, Timmers, HTM, Hahn, S, Devys, D., and L. Tora (2017) SAGA Is a General Cofactor for RNA Polymerase II Transcription. Mol Cell, 68: PMID: Grünberg S, Henikoff S, Hahn S, Zentner GE. (2016). Mediator binding to UASs is broadly uncoupled from transcription and cooperative with TFIID recruitment to promoters. EMBO journal. 35: PMID: Warfield, L., Luo, J., Ranish, J. and S. Hahn (2016). Function of conserved topological regions within the S. cerevisiae basal transcription factor TFIIH. Mol Cell Biol, MCB [Epub ahead of print]. PMID: Hahn, S., and S. Buratowski (2016). (Review) Snapshots of transcription initiation. Nature 331: PMID: Fishburn, J., Galburt, E., and S. Hahn (2016). Transcription start site scanning and the requirement for ATP during transcription initiation by RNA polymerase II. J. Biol Chem, 291: PMID: Luo, J., Cimermancic, P., Viswanath S., Ebmeier, C.C., Kim, B., Dehecq, M, Raman, V., Greenberg, C.H., Pellarin, R., Sali, A., Taatjes, D.J., Hahn, S., and J. Ranish (2015). Architecture of the human and yeast general transcription and DNA repair factor TFIIH. Mol Cell 59: PMID:

8 Fishburn, J., Tomko, E., Galburt, E. and S. Hahn. (2015). Double stranded DNA translocase activity of transcription factor TFIIH and the mechanism of RNA Polymerase II Open Complex formation. Proc Natl Acad Sci USA, 112: PMID: S. Hahn (2014). (Review) Ellis Englesberg and the discovery of positive control in gene regulation. Genetics, 198: PMID: Han, Y., Luo, J., Ranish, J., and S. Hahn (2014). Architecture of the S. cerevisiae SAGA transcription coactivator complex. EMBOJ 33: PMID: Knutson, B., Luo J, Ranish J. and S. Hahn (2014) Architecture of the S. cerevisiae RNA polymerase I Core Factor complex. Nat Struct Mol Biol, 21: PMID: Warfield, L., Tuttle, L.M., Pacheco, D., Klevit, R., and S. Hahn (2014). A sequence-specific transcription activator motif and powerful synthetic variants that bind Mediator using a fuzzy protein interface. Proc Natl Acad Sci USA Aug 26;111(34):E doi: /pnas Epub 2014 Aug 13. PMID: Kamenova, I, Warfield, L. and S. Hahn (2014) Mutations on the DNA binding surface of TBP discriminate between yeast TATA and TATA-less gene transcription. Mol Cell Biol 34: PMID: Grünberg, S. and S. Hahn (2013) Structural insights into transcription initiation by RNA polymerase II (Review). Trends Biochem Sci 38: PMID: Knutson, B.A., and S. Hahn (2012) TFIIB-related factors in RNA polymerase I transcription (Review). Biochimica et Biophysica Acta, 1829: Grünberg S., Warfield, L., and S. Hahn (2012) Architecture of the RNA polymerase II preinitiation complex and mechanism of ATP-dependent promoter opening. Nature Struct Mol Biol, 19: PMID: Luo, J., Fishburn, J., Hahn S., and J. Ranish (2012). An integrated chemical cross-linking and mass spectrometry approach to study protein complex architecture and function. Mol and Cell Proteomics, Feb;11(2):M Epub 2011 Nov 7. PMID: Fishburn, J. and S. Hahn (2011). Architecture of the yeast RNA polymerase II open complex and regulation of activity by TFIIF. Mol Cell Biol, 32: PMID: Brzovic, P.S., Heikaus, C.C, Kisselev, L., Vernon, R., Herbig, E., Pacheco, D., Warfield, L., Littlefield, P., Baker, D., Klevit, R., and S. Hahn (2011). The acidic transcription activator Gcn4 binds the Mediator subunit Gal11/Med15 using a simple protein interface forming a fuzzy complex. Mol Cell, 44: PMID:

9 Hahn S. and E.T. Young (2011) Transcriptional regulation in S. cerevisiae: transcription factor regulation and function, mechanisms of initiation, and roles of activators and coactivators. (YeastBook) Genetics 189: PMID: Knutson, B.A., and S. Hahn (2011). Yeast Rrn7 and human TAF1B are TFIIB-related RNA polymerase I general transcription factors. Science, 333: PMID: Knutson, B.A. and S. Hahn (2011) Domains of Tra1 important for activator recruitment and transcription coactivator functions of SAGA and NuA4 complexes. Mol Cell Biol, 31: PMID: Herbig, E., Warfield, L., Fish, L., Fishburn, J., Knutson, B.A., Moorefield, B., Pacheco, D., and S. Hahn (2010). Mechanism of Mediator recruitment by tandem Gcn4 activation domains and three Gal11 activator-binding domains. Mol Cell Biol 30: PMID: Eichner, J., Chen, H-T., Warfield, L., and S. Hahn. (2010) Position of the general transcription factor TFIIF within the RNA polymerase II transcription preinitiation complex. EMBOJ, 29: PMID: Hahn, S. New beginnings for transcription. (2009) (review) Nature 462: PMID: Liu, Y, Warfield, L., Zhang, C., Luo, J., Allen, J., Lang, W.H., Ranish, J, Shokat, K.M., and S. Hahn (2009) Phosphorylation of the transcription elongation factor Spt5 by yeast Bur1 kinase stimulates recruitment of the PAF complex. Mol Cell Biol 29: PMID: Mohibullah, N. and Hahn, S. (2008) Site-specific cross-linking of TBP in vivo and in vitro reveals a direct functional interaction with the SAGA subunit Spt3. Genes Dev 22: PMID: Lariviere, L., Seizl, M., van Wageningen, S., Rother, S., van de Pasch, L., Feldmann, H., Strasser, K, Hahn, S., Holstege, F.C.P., and P. Cramer (2008). Structure-system correlation identifies a gene regulatory Mediator Submodule. Genes Dev 22: PMID: Kim, B. Nesvizhskii, A.I., Rani, P.G., Hahn, S., Aebersold, R., and Ranish, J.A. (2007). The transcription elongation factor TFIIS is a component of RNA polymerase II preinitiation complexes. Proc Natl Acad Sci USA 104: PMID: Chen H-T, Warfield, L, and S. Hahn (2007). The positions of TFIIF and TFIIE in the RNA polymerase II transcription preinitiation complex. Nat Struct Mol Biol. 14:

10 PMID: Kanin, E.I, Kipp, R.T., Kung, C., Slattery, M., Viale, A., Hahn, S., Shokat, K.M., and Ansari, A.Z. (2007). Chemical inhibition of the TFIIH associated kinase Cdk7/Kin28 does not impair global gene expression. Proc Acad Sci USA 104: PMID: Miller, G. and S. Hahn (2006). A DNA-tethered cleavage probe reveals the path for promoter DNA in the yeast preinitiation complex. Nat Struct Mol Biol. 13: PMID: Reeves, W.M, and S. Hahn. (2005). Targets of the Gal4 transcription activator in functional transcription complexes. Mol Cell Biol. 25: PMID: Fishburn, J., Mohibullah, N., and S. Hahn (2005) Function of a eukaryotic transcription activation domain during the transcription cycle. Mol Cell 18: PMID: Chen H-T. and S. Hahn. (2004) Mapping the location of TFIIB within the RNA Polymerase II transcription preinitiation complex: A model for the structure of the PIC. Cell 119: PMID: Ranish, J.A., Hahn, S., Lu, Y, Yi, E.C., Li, X.J., Eng, J. Aebersold, R. (2004). Identification of Tfb5, a new component of general transcription and DNA repair factor IIH. Nat. Genet. 36: PMID: Warfield, L, Ranish, J.A. and S. Hahn (2004). Positive and negative functions of the SAGA complex mediated through interaction of spt8 with TBP and the N-terminal domain of TFIIA. Genes Dev. 18: PMID: Hahn, S. (2004). Structure and Mechanism of the RNA Polymerase II transcription machinery (Review). Nat Struct Mol Biol. 11: PMID: Liu, Y., C. Kung, A.Z. Ansari, K.M. Shokat, and S. Hahn. (2004). Two cyclin-dependent kinases promote RNA polymerase II transcription initiation and formation of the Scaffold Complex. Mol Cell Biol 24: PMID: Rani, P.G., Ranish, J.A., and S. Hahn. (2004). The Pol II-TFIIF and Pol II-Mediator complexes: the major stable RNA polymerase II complexes and their activity in transcription initiation and reinitiation. Mol Cell Biol 24: PMID: Chen, H-T. and S. Hahn. (2003). Identification of the binding site for the TFIIB zinc ribbon domain on RNA Polymerase II. Mol Cell 12: PMID: Reeves, W.M. and S. Hahn. (2003). Activator-independent functions of the yeast Mediator Sin4 complex in reinitiation complex formation and transcription reinitiation. 10

11 Mol Cell Biol. 23: PMID: Liu, Y., Ranish, J.A., Aebersold, R., and S. Hahn. (2001). Yeast nuclear extract contains two major forms of RNA Polymerase II Mediator Complexes. J. Biol. Chem, 276: PMID: Yudkovsky, N. Ranish, J.A., and S. Hahn. (2000) A transcription reinitiation intermediate that is stabilized by activator. Nature 408: PMID: Hahn, S. and S. Roberts. (2000) The zinc ribbon domains of the general transcription factors TFIIB and Brf: Conserved functional surfaces but different roles in transcription initiation. Genes Dev. 14: PMID: Yudkovsky, N., Logie, C., Hahn, S., Peterson, C.L. (1999). Recruitment of the SWI/SNF chromatin remodeling complex by transcriptional activators. Genes Dev. 13: PMID: Ranish, J.A., Yudkovsky, N., and S. Hahn. (1999). Intermediates in formation and activity of the RNA polymerase II preinitiation complex: holoenzyme recruitment and a postrecruitment role for the TATA box and TFIIB. Genes and Dev. 13: PMID: Hahn S. (1998). The role of TAFs in RNA Polymerase II transcription. Cell 95: PMID: Hahn, S. (1998). Activation and the role of reinitiation in the control of transcription by RNA Polymerase II. Cold Spring Harbor Symp. Quant. Biol. LXIII: PMID: Colbert, T., Lee, S., Schimmack, G., and S. Hahn. (1998). Architecture of protein and DNA contacts within the TFIIIB-DNA complex. Mol. Cell. Biol. 18: PMID: Auble, D.T., Wang, D., Post, K.W., and S. Hahn. (1997). Molecular analysis of the SNF2/SWI2 protein family member MOT1, an ATP-driven TBP-DNA dissociating enzyme. Mol Cell. Biol 17: PMID: Geiger, J.H., Hahn, S., Lee, S., Sigler, P.B. (1996). The crystal structure of the yeast TFIIA/TBP/DNA complex. Science, 272: PMID: Roberts, S., Miller, S.J., Lane, W.S., Lee, S., and S. Hahn. (1996). Cloning and functional characterization of the gene encoding the TFIIIB90 subunit of RNA polymerase III transcription factor TFIIIB. J. Biol. Chem., 271: PMID:

12 Ranish, J.A., and S. Hahn. (1996), Transcription: basal factors and activation. Curr. Op Genetics and Dev. 6: (review) PMID: Hahn, S. (1995). Clamping the TBP stirrup. Nature 377: (News and Views). Lee, S. and S. Hahn. (1995). Model for binding of transcription factor TFIIB to the TBP- DNA complex. Nature, 376: PMID: Roberts, S., Colbert, T., and S. Hahn. (1995). TFIIIC determines RNA polymerase III specificity at the TATA-containing yeast U6 promoter. Genes and Dev. 9: PMID: Kang, J.J., Auble, D.T., Ranish, J.A., and S. Hahn. (1995). Analysis of the yeast transcription factor TFIIA: distinct functional regions and a polymerase II-specific role in basal and activated transcription. Mol Cell Biol. 15: PMID: Auble, D.T., Hansen, K.E., Mueller, C.G.F., Lane, W.S., Thorner, J., and S. Hahn. (1994). Mot1, a global repressor of RNA polymerase II transcription, inhibits TBP binding to DNA by an ATP-dependent mechanism. Genes and Development 8: PMID: Kim, Y., Geiger, J.H., Hahn, S. and Sigler, P.B. (1993). Crystal structure of a yeast TBP/TATA-box complex. Nature 365: PMID: Hahn, S. (1993). Efficiency in activation. Nature 363: (News and Views). Hahn, S (1993). Structure (?) and function of acidic transcription activators. Cell 72, (minireview) PMID: Auble, D.T. and S. Hahn (1993). An ATP-dependent inhibitor of TBP binding to DNA. Genes and Dev. 7: PMID: PMID: Kassavetis, G.A., Joazeiro, C.A., Blanco, J.A., Pisano, M., Colbert, T. Hahn, S., and E.P. Geiduschek (1992). The Role of the TATA-binding protein in the assembly and function of the multisubunit yeast RNA polymerase III transcription factor TFIIIB. Cell 71: PMID: Colbert, T. and S. Hahn (1992). A yeast TFIIB related factor involved in RNA polymerase III transcription. Genes and Dev. 6: PMID: Schultz, M.C., Reeder, R.H., and S. Hahn (1992). Variants of the TATA-binding protein can distinguish subsets of RNA polymerase I, II, and III promoters. Cell: 69, PMID:

13 Ranish, J., Lane, W.S., and S. Hahn (1992). Isolation of two genes that encode subunits of the yeast transcription factor IIA. Science 255: PMID: Ranish, J. and S. Hahn (1991). The yeast general transcription factor TFIIA is composed of two polypeptide subunits. J. Biol. Chem 266: PMID: Reddy P. and S. Hahn (1991). Dominant negative mutations in yeast TFIID define a bipartite DNA binding region. Cell 65: PMID: Hahn, S., Buratowski, S., Sharp, P.A., and L. Guarente (1989). Isolation of the gene encoding the yeast TATA binding protein TFIID: a gene identical to the SPT15 suppressor of Ty element insertions. Cell 58: PMID: Hahn, S., Buratowski, S., Sharp, P.A., and L. Guarente (1989). Identification of a yeast protein homologous in function to the mammalian general transcription factor, TFIIA. EMBO J. 8: PMID: Hahn, S. Buratowski, S., Sharp, P.A., and L. Guarente (1989). Yeast TATA-binding protein TFIID binds to TATA elements with both consensus and nonconsensus DNA sequences. Proc. Natl. Acad. Sci. USA 86: PMID: Buratowski, S., Hahn, S., Guarente, L., and P.A. Sharp (1989). Five Intermediate Complexes in Transcription Initiation by RNA Polymerase II. Cell 56: PMID: Buratowski, S., Hahn, S., Sharp, P.A., and L. Guarente (1988) Function of a yeast TATA element-binding protein in a mammalian transcription system. Nature 334: PMID: Chodosh. L., Olesen, J, Hahn, S., Baldwin, A.S., Guarente, L. and P.A. Sharp (1988) A yeast and human CCAAT-binding protein have heterologous subunits that are functionally interchangeable. Cell 53: PMID: Hahn, S. and L. Guarente (1988). Yeast HAP2 and HAP3: Transcriptional activators in a Heteromeric complex. Science 240: PMID: Hahn, S., Pinkham, J., Wei, R., Miller, R., and L. Guarente. (1988) The HAP3 regulatory gene from S. cerevisiae encodes divergent overlapping transcripts. Mol. Cell. Biol. 8: PMID: Olesen, J., Hahn, S., and L. Guarente. (1987) Yeast HAP2 and HAP3 activators both bind to the CYC1 upstream activation site UAS2 in an interdependent manner. Cell 51: PMID:

14 Hahn, S., Hoar, E., and L. Guarente. (1985) Three Functional TATA Elements Contribute to Transcription Initiation from the CYC1 gene in S. cerevisiae. Proc. Natl. Acad. Sci. USA 82: PMID: Hahn, S., Hendrickson, W., and R. Schleif. (1986) Transcription of Escherichia coli ara in vitro: The Cyclic AMP Receptor Protein Requirement for PBAD Induction that Depends on the Presence and Orientation of the arao2 site. J. Mol. Biol. 188: PMID: Hahn, S. (1984). Studies on Transcriptional Regulation of the Escherichia coli L- arabinose Operon. Ph.D. Thesis, Brandeis University. Hahn, S., Dunn, T., and R. Schleif. (1984) Repression and CRP Stimulation of the arabad Promoter in vivo. J. Mol. Biol. 180: PMID: Dunn, T., Hahn, S., Ogden, S., and Schleif, R. (1984) An operator at -280 base pairs that is required for repression of arabad operon promoter: addition of DNA helical turns between the operator and promoter cyclically hinders repression. Proc. Natl. Acad. Sci. USA 81: PMID: Hahn, S. and R. Schleif. (1983) In vivo Regulation of the Escherichia coli arac Promoter. J. Bacteriol. 155: PMID: