Stephen Buratowski

Stephen Buratowski

Professor of Biological Chemistry and Moelcular Pharmacology
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Member, Harvard Center for Cancer Research
SBuratowski Photo

The Buratowski Lab studies eukaryotic gene transcription, chromatin regulation, and RNA processing using a wide range of biochemical, molecular, and genetic techniques.

The Buratowski Lab studies eukaryotic gene expression, concentrating on RNA polymerase II transcription and its coupling to RNA processing and chromatin modification.  Much of our work centers on the C-terminal domain (CTD) of the Rpb1, the largest polymerase subunit. A dynamic pattern of differential phosphorylations act to mark polymerases at the initiation, early elongation, and late elongation stages.  The mRNA capping enzyme and the histone H3K4 methyltransferase Set1 recognize the early phosphorylation pattern, while polyadenylation factors and the H3K36 methyltransferase Set2 binds the late CTD pattern. Much of this “CTD cycle” model is based on in vivo crosslinking, so a true understanding of the system dynamics will require more sophisticated methods. Towards this goal, we have adapted two technologies to our in vitro transcription system: time-resolved quantitative mass spectrometry and single-molecule TIRF microscopy. Combined with classic molecular genetics and genomics, these approaches are providing new insights into the kinetic and thermodynamic control of gene expression.

Selected Publications:

T. Kim, Z. Xu, S. Clauder-Munster, L.M. Steinmetz, and S. Buratowski. 
Set3 HDAC mediates effects of overlapping noncoding transcription on gene induction kinetics.  Cell 150(6):1158-69 (2012)
 
S. Marquardt, R. Escalante-Chong, N. Pho, J. Wang, L.S. Churchman, M. Springer, and S. Buratowski
A chromatin-based mechanism for limiting divergent non-coding transcription.  Cell 157, 1712-1723 (2014)
 
H. Suh, S.B. Ficarro, U.B. Kang, Y. Chun, J.A. Marto, and S. Buratowski

Direct analysis of phosphorylation sites on the Rpb1 C-terminal domain of RNA polymerase II. Mol. Cell 61, 297-304 (2016)

 
L. M. Soares, P.C. He, Y. Chun, H. Suh, T.S. Kim, and S. Buratowski
Determinants of histone H3K4 methylation.  Molecular Cell 68, 772-785 (2017)
 
Y.J. Joo, S.B. Ficarro, L.M. Soares, Y. Chun, J.A. Marto, and S. Buratowski
Downstream promoter interactions of TFIID TAFs facilitate transcription reinitiation.  Genes Dev. 31, 2162-2174 (2017)
 
D.J.M. du Mee, M. Ivanov, J.P. Parker, S. Buratowski, and S. Marquardt
Efficient termination of nuclear lncRNA transcription promotes mitochondrial genome maintenance.  eLife 7, e31989 (2018)
 
H.E. Mischo, Y. Chin, K.M. Harlen, S. Dhir, L.S. Churchman, and S. Buratowski
Cell-cycle modulation of transcription termination factor Sen1.  Molecular Cell 70, 312-326 (2018)

 

Contact Information

Building C1, Room 210
Harvard Medical School
240 Longwood Avenue
Boston, MA 02115
p: 617 432-0696