Photo of Stephen Buratowski,  PhD

Stephen Buratowski, PhD

Harvard Medical School

Harvard Medical School
Phone: (617) 432-0696
Fax: (617) 738-0516

Stephen Buratowski, PhD

Harvard Medical School


  • Professor, Biological Chemistry and Molecular Pharmacology, Harvard Medical School


Research Abstract

We study the mechanism of eukaryotic gene expression using the yeast

Saccharomyces cerevisiae as a model system. Biochemical, molecular, and

genetic techniques are used to study the basal and regulatory transcription

factors required for proper RNA polymerase II transcription initiation and termination. We also study mRNA modifications such as capping and polyadenylation. We have shown that coupling of these processes with transcription is mediated by the association of various enzymes with different phosphorylated forms of RNA polymerase II. More recently, we have been studying how this phosphorylation system sets up a characteristic pattern of histone methylation on genes. We study the downstream effects of these histone modifications on gene expression. Importantly, many of the enzymes involved in these processes turn out to be mutated in human cancers.


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  • Marquardt S, Escalante-Chong R, Pho N, Wang J, Churchman LS, Springer M, Buratowski S. A chromatin-based mechanism for limiting divergent noncoding transcription. Cell 2014; 157:1712-23. PubMed
  • Soares LM, Radman-Livaja M, Lin SG, Rando OJ, Buratowski S. Feedback Control of Set1 Protein Levels Is Important for Proper H3K4 Methylation Patterns. Cell Rep 2014; 6:961-72. PubMed
  • Heo DH, Yoo I, Kong J, Lidschreiber M, Mayer A, Choi BY, Hahn Y, Cramer P, Buratowski S, Kim M. The RNA polymerase II C-terminal domain-interacting domain of yeast Nrd1 contributes to the choice of termination pathway and couples to RNA processing by the nuclear exosome. J Biol Chem 2013; 288:36676-90. PubMed
  • Suh H, Hazelbaker DZ, Soares LM, Buratowski S. The C-terminal domain of Rpb1 functions on other RNA polymerase II subunits. Mol Cell 2013; 51:850-8. PubMed
  • Soares LM, Buratowski S. Histone Crosstalk: H2Bub and H3K4 Methylation. Mol Cell 2013; 49:1019-20. PubMed
  • Fowler T, Suh H, Buratowski S, Roy AL. Regulation of primary response genes in B cells. J Biol Chem 2013. PubMed
  • Hazelbaker DZ, Marquardt S, Wlotzka W, Buratowski S. Kinetic competition between RNA Polymerase II and Sen1-dependent transcription termination. Mol Cell 2013; 49:55-66. PubMed
  • Hazelbaker DZ, Buratowski S. Transcription: base j blocks the way. Curr Biol 2012; 22:R960-2. PubMed
  • Sikorski TW, Joo YJ, Ficarro SB, Askenazi M, Buratowski S, Marto JA. Proteomic Analysis Demonstrates Activator- and Chromatin-specific Recruitment to Promoters. J Biol Chem 2012; 287:35397-408. PubMed
  • van Werven FJ, Neuert G, Hendrick N, Lardenois A, Buratowski S, van Oudenaarden A, Primig M, Amon A. Transcription of two long noncoding RNAs mediates mating-type control of gametogenesis in budding yeast. Cell 2012; 150:1170-81. PubMed
  • Kim T, Xu Z, Clauder-M√ľnster S, Steinmetz LM, Buratowski S. Set3 HDAC mediates effects of overlapping noncoding transcription on gene induction kinetics. Cell 2012; 150:1158-69. PubMed
  • Radman-Livaja M, Quan TK, Valenzuela L, Armstrong JA, van Welsem T, Kim T, Lee LJ, Buratowski S, van Leeuwen F, Rando OJ, Hartzog GA. A key role for Chd1 in histone H3 dynamics at the 3' ends of long genes in yeast. PLoS Genet. 2012; 8:e1002811. PubMed
  • Soares LM, Buratowski S. Yeast Swd2 is essential due to antagonism between the Set1 histone methyltransferase complex and the Associated with Pta1 (APT) termination factor. J Biol Chem 2012. PubMed
  • Buratowski S. Gene expression: transcription initiation unwrapped. Nature 2012; 483:286-7. PubMed
  • Weiner A, Chen HV, Liu CL, Rahat A, Klien A, Soares L, Gudipati M, Pfeffner J, Regev A, Buratowski S, Pleiss JA, Friedman N, Rando OJ. Systematic dissection of roles for chromatin regulators in a yeast stress response. PLoS Biol. 2012; 10:e1001369. PubMed
  • Sikorski TW, Ficarro SB, Holik J, Kim T, Rando OJ, Marto JA, Buratowski S. Sub1 and RPA associate with RNA polymerase II at different stages of transcription. Mol Cell 2011; 44:397-409. PubMed
  • Terzi N, Churchman LS, Vasiljeva L, Weissman J, Buratowski S. H3K4 trimethylation by Set1 promotes efficient termination by the Nrd1-Nab3-Sen1 pathway. Mol Cell Biol 2011; 31:3569-83. PubMed
  • Lenstra TL, Benschop JJ, Kim T, Schulze JM, Brabers NA, Margaritis T, van de Pasch LA, van Heesch SA, Brok MO, Groot Koerkamp MJ, Ko CW, van Leenen D, Sameith K, van Hooff SR, Lijnzaad P, Kemmeren P, Hentrich T, Kobor MS, Buratowski S, Holstege FC. The specificity and topology of chromatin interaction pathways in yeast. Mol Cell 2011; 42:536-49. PubMed
  • Marquardt S, Hazelbaker DZ, Buratowski S. Distinct RNA degradation pathways and 3' extensions of yeast non-coding RNA species. Transcr 2011; 2:145-154. PubMed
  • Dermody JL, Buratowski S. Leo1 subunit of the yeast paf1 complex binds RNA and contributes to complex recruitment. J Biol Chem 2010; 285:33671-9. PubMed
  • Lunde BM, Reichow SL, Kim M, Suh H, Leeper TC, Yang F, Mutschler H, Buratowski S, Meinhart A, Varani G. Cooperative interaction of transcription termination factors with the RNA polymerase II C-terminal domain. Nat Struct Mol Biol 2010; 17:1195-201. PubMed
  • Kim TS, Liu CL, Yassour M, Holik J, Friedman N, Buratowski S, Rando OJ. RNA polymerase mapping during stress responses reveals widespread nonproductive transcription in yeast. Genome Biol 2010; 11:R75. PubMed
  • Buratowski S. Progression through the RNA polymerase II CTD cycle. Mol Cell 2009; 36:541-6. PubMed
  • Kim M, Suh H, Cho EJ, Buratowski S. Phosphorylation of the yeast Rpb1 C-terminal domain at serines 2, 5, and 7. J Biol Chem 2009; 284:26421-6. PubMed
  • Johnson A, Li G, Sikorski TW, Buratowski S, Woodcock CL, Moazed D. Reconstitution of heterochromatin-dependent transcriptional gene silencing. Mol Cell 2009; 35:769-81. PubMed
  • Sikorski TW,Buratowski S. The basal initiation machinery: beyond the general transcription factors. Curr Opin Cell Biol 2009; 21:344-51. PubMed
  • Kim T,Buratowski S. Dimethylation of H3K4 by Set1 recruits the Set3 histone deacetylase complex to 5' transcribed regions. Cell 2009; 137:259-72. PubMed
  • Ahn SH,Keogh MC,Buratowski S. Ctk1 promotes dissociation of basal transcription factors from elongating RNA polymerase II. EMBO J 2009; 28:205-12. PubMed
  • Buratowski S. Transcription. Gene expression--where to start? Science 2008; 322:1804-5. PubMed
  • Vasiljeva L,Kim M,Mutschler H,Buratowski S,Meinhart A. The Nrd1-Nab3-Sen1 termination complex interacts with the Ser5-phosphorylated RNA polymerase II C-terminal domain. Nat Struct Mol Biol 2008; 15:795-804. PubMed
  • Runner VM, Podolny V, Buratowski S. The Rpb4 subunit of RNA polymerase II contributes to cotranscriptional recruitment of 3' processing factors. Mol Cell Biol 2008; 28:1883-91. PubMed
  • Vasiljeva L, Kim M, Terzi N, Soares LM, Buratowski S. Transcription termination and RNA degradation contribute to silencing of RNA polymerase II transcription within heterochromatin. Mol Cell 2008; 29:313-23. PubMed
  • Deka P, Bucheli ME, Moore C, Buratowski S, Varani G. Structure of the yeast SR protein Npl3 and Interaction with mRNA 3'-end processing signals. J Mol Biol 2007; 375:136-50. PubMed
  • Dermody JL,Dreyfuss JM,Villen J,Ogundipe B,Gygi SP,Park PJ,Ponticelli AS,Moore CL,Buratowski S,Bucheli ME. Unphosphorylated SR-like protein Npl3 stimulates RNA polymerase II elongation. PLoS ONE 2008; 3:e3273. PubMed
  • Bucheli ME, He X, Kaplan CD, Moore CL, Buratowski S. Polyadenylation site choice in yeast is affected by competition between Npl3 and polyadenylation factor CFI. RNA 2007; 13:1756-64. PubMed
  • Huarte M, Lan F, Kim T, Vaughn MW, Zaratiegui M, Martienssen RA, Buratowski S, Shi Y. The fission yeast Jmj2 reverses histone H3 Lysine 4 trimethylation. J Biol Chem 2007; 282:21662-70. PubMed
  • Kim T, Buratowski S. Two Saccharomyces cerevisiae JmjC domain proteins demethylate histone H3 Lys36 in transcribed regions to promote elongation. J Biol Chem 2007; 282:20827-35. PubMed
  • Keogh MC, Mennella TA, Sawa C, Berthelet S, Krogan NJ, Wolek A, Podolny V, Carpenter LR, Greenblatt JF, Baetz K, Buratowski S. The Saccharomyces cerevisiae histone H2A variant Htz1 is acetylated by NuA4. Genes Dev 2006; 20:660-5. PubMed
  • Keogh MC, Kim JA, Downey M, Fillingham J, Chowdhury D, Harrison JC, Onishi M, Datta N, Galicia S, Emili A, Lieberman J, Shen X, Buratowski S, Haber JE, Durocher D, Greenblatt JF, Krogan NJ. A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. Nature 2005; 439:497-501. PubMed
  • Vasiljeva L, Buratowski S. Nrd1 interacts with the nuclear exosome for 3' processing of RNA polymerase II transcripts. Mol Cell 2006; 21:239-48. PubMed
  • Chowdhury D, Keogh MC, Ishii H, Peterson CL, Buratowski S, Lieberman J. gamma-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair. Mol Cell 2005; 20:801-9. PubMed
  • Keogh MC, Kurdistani SK, Morris SA, Ahn SH, Podolny V, Collins SR, Schuldiner M, Chin K, Punna T, Thompson NJ, Boone C, Emili A, Weissman JS, Hughes TR, Strahl BD, Grunstein M, Greenblatt JF, Buratowski S, Krogan NJ. Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell 2005; 123:593-605. PubMed
  • Liu CL, Kaplan T, Kim M, Buratowski S, Schreiber SL, Friedman N, Rando OJ. Single-nucleosome mapping of histone modifications in S. cerevisiae. PLoS Biol 2005; 3:e328. PubMed
  • Buratowski S, Moazed D. Gene regulation: expression and silencing coupled. Nature 2005; 435:1174-5. PubMed
  • Bucheli ME, Buratowski S. Npl3 is an antagonist of mRNA 3' end formation by RNA polymerase II. EMBO J 2005; 24:2150-60. PubMed
  • Buratowski S. Connections between mRNA 3' end processing and transcription termination. Curr Opin Cell Biol 2005; 17:257-61. PubMed
  • Krogan NJ, Lam MH, Fillingham J, Keogh MC, Gebbia M, Li J, Datta N, Cagney G, Buratowski S, Emili A, Greenblatt JF. Proteasome involvement in the repair of DNA double-strand breaks. Mol Cell 2004; 16:1027-34. PubMed
  • Auty R, Steen H, Myers LC, Persinger J, Bartholomew B, Gygi SP, Buratowski S. Purification of active TFIID from Saccharomyces cerevisiae. Extensive promoter contacts and co-activator function. J Biol Chem 2004; 279:49973-81. PubMed
  • Kim M, Krogan NJ, Vasiljeva L, Rando OJ, Nedea E, Greenblatt JF, Buratowski S. The yeast Rat1 exonuclease promotes transcription termination by RNA polymerase II. Nature 2004; 432:517-22. PubMed
  • Krogan NJ, Baetz K, Keogh MC, Datta N, Sawa C, Kwok TC, Thompson NJ, Davey MG, Pootoolal J, Hughes TR, Emili A, Buratowski S, Hieter P, Greenblatt JF. Regulation of chromosome stability by the histone H2A variant Htz1, the Swr1 chromatin remodeling complex, and the histone acetyltransferase NuA4. Proc Natl Acad Sci U S A 2004; 101:13513-8. PubMed
  • Sawa C, Nedea E, Krogan N, Wada T, Handa H, Greenblatt J, Buratowski S. Bromodomain factor 1 (Bdf1) is phosphorylated by protein kinase CK2. Mol Cell Biol 2004; 24:4734-42. PubMed
  • Kim M, Ahn SH, Krogan NJ, Greenblatt JF, Buratowski S. Transitions in RNA polymerase II elongation complexes at the 3' ends of genes. EMBO J 2004; 23:354-64. PubMed
  • Ahn SH, Kim M, Buratowski S. Phosphorylation of serine 2 within the RNA polymerase II C-terminal domain couples transcription and 3' end processing. Mol Cell 2004; 13:67-76. PubMed
  • Matangkasombut O, Auty R, Buratowski S. Structure and function of the TFIID complex. Adv Protein Chem 2004; 67:67-92. PubMed
  • Keogh MC, Buratowski S. Using chromatin immunoprecipitation to map cotranscriptional mRNA processing in Saccharomyces cerevisiae. Methods Mol Biol 2004; 257:1-16. PubMed
  • Krogan NJ, Keogh MC, Datta N, Sawa C, Ryan OW, Ding H, Haw RA, Pootoolal J, Tong A, Canadien V, Richards DP, Wu X, Emili A, Hughes TR, Buratowski S, Greenblatt JF. A Snf2 family ATPase complex required for recruitment of the histone H2A variant Htz1. Mol Cell 2003; 12:1565-76. PubMed
  • Keogh MC, Podolny V, Buratowski S. Bur1 kinase is required for efficient transcription elongation by RNA polymerase II. Mol Cell Biol 2003; 23:7005-18. PubMed
  • Buratowski S. The CTD code. Nat Struct Biol 2003; 10:679-80. PubMed
  • Nedea E, He X, Kim M, Pootoolal J, Zhong G, Canadien V, Hughes T, Buratowski S, Moore CL, Greenblatt J. Organization and function of APT, a subcomplex of the yeast cleavage and polyadenylation factor involved in the formation of mRNA and small nucleolar RNA 3'-ends. J Biol Chem 2003; 278:33000-10. PubMed
  • Krogan NJ, Kim M, Tong A, Golshani A, Cagney G, Canadien V, Richards DP, Beattie BK, Emili A, Boone C, Shilatifard A, Buratowski S, Greenblatt J. Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II. Mol Cell Biol 2003; 23:4207-18. PubMed
  • Takagi T, Walker AK, Sawa C, Diehn F, Takase Y, Blackwell TK, Buratowski S. The Caenorhabditis elegans mRNA 5'-capping enzyme. In vitro and in vivo characterization. J Biol Chem 2003; 278:14174-84. PubMed
  • Matangkasombut O, Buratowski S. Different sensitivities of bromodomain factors 1 and 2 to histone H4 acetylation. Mol Cell 2003; 11:353-63. PubMed
  • Buratowski RM, Downs J, Buratowski S. Interdependent interactions between TFIIB, TATA binding protein, and DNA. Mol Cell Biol 2002; 22:8735-43. PubMed
  • Krogan NJ, Kim M, Ahn SH, Zhong G, Kobor MS, Cagney G, Emili A, Shilatifard A, Buratowski S, Greenblatt JF. RNA polymerase II elongation factors of Saccharomyces cerevisiae: a targeted proteomics approach. Mol Cell Biol 2002; 22:6979-92. PubMed
  • Takagi T, Cho EJ, Janoo RT, Polodny V, Takase Y, Keogh MC, Woo SA, Fresco-Cohen LD, Hoffman CS, Buratowski S. Divergent subunit interactions among fungal mRNA 5'-capping machineries. Eukaryot Cell 2002; 1:448-57. PubMed
  • Keogh MC, Cho EJ, Podolny V, Buratowski S. Kin28 is found within TFIIH and a Kin28-Ccl1-Tfb3 trimer complex with differential sensitivities to T-loop phosphorylation. Mol Cell Biol 2002; 22:1288-97. PubMed
  • Cho EJ, Kobor MS, Kim M, Greenblatt J, Buratowski S. Opposing effects of Ctk1 kinase and Fcp1 phosphatase at Ser 2 of the RNA polymerase II C-terminal domain. Genes Dev 2001; 15:3319-29. PubMed
  • Selleck W, Howley R, Fang Q, Podolny V, Fried MG, Buratowski S, Tan S. A histone fold TAF octamer within the yeast TFIID transcriptional coactivator. Nat Struct Biol 2001; 8:695-700. PubMed
  • Takagi T, Buratowski S. A Plasmodium falciparum protein related to fungal RNA 5'-triphosphatases. Mol Biochem Parasitol 2001; 114:239-44. PubMed
  • Takase Y, Takagi T, Komarnitsky PB, Buratowski S. The essential interaction between yeast mRNA capping enzyme subunits is not required for triphosphatase function in vivo. Mol Cell Biol 2000; 20:9307-16. PubMed
  • Komarnitsky P, Cho EJ, Buratowski S. Different phosphorylated forms of RNA polymerase II and associated mRNA processing factors during transcription. Genes Dev 2000; 14:2452-60. PubMed
  • Buratowski S. Snapshots of RNA polymerase II transcription initiation. Curr Opin Cell Biol 2000; 12:320-5. PubMed
  • Matangkasombut O, Buratowski RM, Swilling NW, Buratowski S. Bromodomain factor 1 corresponds to a missing piece of yeast TFIID. Genes Dev 2000; 14:951-62. PubMed
  • Rodriguez CR, Cho EJ, Keogh MC, Moore CL, Greenleaf AL, Buratowski S. Kin28, the TFIIH-associated carboxy-terminal domain kinase, facilitates the recruitment of mRNA processing machinery to RNA polymerase II. Mol Cell Biol 1999; 20:104-12. PubMed
  • Morehouse H, Buratowski RM, Silver PA, Buratowski S. The importin/karyopherin Kap114 mediates the nuclear import of TATA-binding protein. Proc Natl Acad Sci U S A 1999; 96:12542-7. PubMed
  • Komarnitsky PB, Michel B, Buratowski S. TFIID-specific yeast TAF40 is essential for the majority of RNA polymerase II-mediated transcription in vivo. Genes Dev 1999; 13:2484-9. PubMed
  • Deshpande T, Takagi T, Hao L, Buratowski S, Charbonneau H. Human PIR1 of the protein-tyrosine phosphatase superfamily has RNA 5'-triphosphatase and diphosphatase activities. J Biol Chem 1999; 274:16590-4. PubMed
  • Rodriguez CR, Takagi T, Cho EJ, Buratowski S. A Saccharomyces cerevisiae RNA 5'-triphosphatase related to mRNA capping enzyme. Nucleic Acids Res 1999; 27:2181-8. PubMed
  • Cho EJ, Rodriguez CR, Takagi T, Buratowski S. Allosteric interactions between capping enzyme subunits and the RNA polymerase II carboxy-terminal domain. Genes Dev 1998; 12:3482-7. PubMed
  • Michel B, Komarnitsky P, Buratowski S. Histone-like TAFs are essential for transcription in vivo. Mol Cell 1998; 2:663-73. PubMed
  • Cho EJ, Takagi T, Moore CR, Buratowski S. mRNA capping enzyme is recruited to the transcription complex by phosphorylation of the RNA polymerase II carboxy-terminal domain. Genes Dev 1998; 11:3319-26. PubMed
  • Kuldell NH, Buratowski S. Genetic analysis of the large subunit of yeast transcription factor IIE reveals two regions with distinct functions. Mol Cell Biol 1997; 17:5288-98. PubMed
  • Takagi T, Moore CR, Diehn F, Buratowski S. An RNA 5'-triphosphatase related to the protein tyrosine phosphatases. Cell 1997; 89:867-73. PubMed
  • Moqtaderi Z, Yale JD, Struhl K, Buratowski S. Yeast homologues of higher eukaryotic TFIID subunits. Proc Natl Acad Sci U S A 1996; 93:14654-8. PubMed
  • Fresco LD, Buratowski S. Conditional mutants of the yeast mRNA capping enzyme show that the cap enhances, but is not required for, mRNA splicing. RNA 1996; 2:584-96. PubMed
  • Matsui P, DePaulo J, Buratowski S. An interaction between the Tfb1 and Ssl1 subunits of yeast TFIIH correlates with DNA repair activity. Nucleic Acids Res 1995; 23:767-72. PubMed
  • Fresco LD, Buratowski S. Active site of the mRNA-capping enzyme guanylyltransferase from Saccharomyces cerevisiae: similarity to the nucleotidyl attachment motif of DNA and RNA ligases. Proc Natl Acad Sci U S A 1994; 91:6624-8. PubMed
  • Buratowski S, Zhou H. Functional domains of transcription factor TFIIB. Proc Natl Acad Sci U S A 1993; 90:5633-7. PubMed
  • Buratowski S, Zhou H. A suppressor of TBP mutations encodes an RNA polymerase III transcription factor with homology to TFIIB. Cell 1992; 71:221-30. PubMed