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

EDUCATIONAL TITLES

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

DF/HCC PROGRAM AFFILIATION

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.

Publications

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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
  • Fowler T, Suh H, Buratowski S, Roy AL. Regulation of primary response genes in B cells. J Biol Chem 2013. PubMed
  • Soares LM, Buratowski S. Histone Crosstalk: H2Bub and H3K4 Methylation. Mol Cell 2013; 49:1019-20. 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
  • 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
  • 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
  • Soares LM, Buratowski S. Yeast Swd2 is essential because of antagonism between Set1 histone methyltransferase complex and APT (associated with Pta1) 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
  • 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
  • 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
  • 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
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