Our laboratory studies the regulation of gene expression in eukaryotic organisms.
The experimental organism used in most of our work is the yeast
Saccharomyces cerevisiae, which enables us to use a powerful combination of
classical genetics, modern biochemistry and genomics/proteomics in our studies.
We have three principal interests. One is to define the mechanism of
transcription initiation by RNA polymerase II (RNAP II) and how transcription is
regulated. A focus of this work is the general transcription factor TFIIB and its
role in (i) assembly of the preinitiation complex; (ii) transcription initiation and
promoter clearance; and (iii) transcription reinitiation.
A second interest is the relationship between transcription and mRNA 3’-end
formation. Our genetic analysis of TFIIB uncovered a novel factor, Ssu72, that
we recently found to be an RNAP II CTD phosphatase with specificity for serine5-P. Interestingly, Ssu72 is an essential component of the pre-mRNA 3’-end
processing machinery, although this function is independent of phosphatase
activity. Current efforts are directed toward understanding the connection
between transcription initiation, CTD phosphorylation/dephosphorylation, and 3’end formation.
Our third interest is the role of chromatin structure in regulating gene expression.
We have identified histone acetyl transferases and deacetylases that affect gene
expression in a position-dependent, promoter-independent (silencing) manner.
More recently, we have identified histone methyltransferases that also affect
silencing. We are especially interested to know how these and other covalent
histone modifications affect accessibility of chromatin to the transcriptional
machinery.
A remarkable feature of the general transcription factors, including cofactors that
affect chromatin structure, is the extent to which these factors are conserved
among eukaryotic organisms. Thus, we are able to use an extensive arsenal of
experimental approaches to address fundamental questions pertaining to gene
expression, with result from one system applicable to other systems. Moreover,
we are able to learn about these processes both in vitro and in vivo.
Selected Publications:
KRISHNAMURTHY, S., X. HE, M. REYES-REYES, C. MOORE and M.
HAMPSEY (2004) Ssu72 is a novel RNA polymerase II CTD phosphatase [in
press].
CHEN, B.-S. and M. HAMPSEY (2004) Functional interaction between TFIIB
and the Rpb2 subunit of RNA polymerase II: implications for the mechanism of
transcription start site selection. Mol. Cell Biol. 24:3983-3991.
HAMPSEY, M. and D. REINBERG (2003) Tails of intrigue: phosphorylation of
RNA polymerase II mediates histone methylation. Cell 113:429-432.
HE, X., A.U. KHAN, H. CHENG, D.L. PAPPAS, M. HAMPSEY and C.L. MOORE
(2003) Functional interactions between the transcription and mRNA 3' end
processing machineries mediated by Ssu72 and Sub1. Genes Dev. 17:10301042.
CHEN, B.S. and M. HAMPSEY (2002) Transcription activation: unveiling the
essential nature of TFIID. Curr Biol. 12:R620-622.
KHAN, A.U. and M. HAMPSEY (2002) Connecting the DOTs: covalent histone
modifications and the formation of silent chromatin. Trends Genet. 18:387-389.
WOYCHIK, N.A. and M. HAMPSEY (2002) The RNA polymerase II machinery:
structure illuminates function. Cell 108:453-463.
CHEN, B.-S., Z.-W. SUN and M. HAMPSEY (2001) A Gal4-s54 hybrid protein
that functions as a potent activator of RNA polymerase II transcription in yeast. J.
Biol. Chem. 276:23881-23887.
PAPPAS, D.L. and M. HAMPSEY (2000) Functional interaction between Ssu72
and the Rpb2 subunit of RNA polymerase II in Saccharomyces cerevisiae. Mol.
Cell. Biol. 20:8343-8351.
HAMPSEY, M. (1998) Molecular genetics of the RNA polymerase II general
transcriptional machinery. Microbiol. Molec. Biol. Rev. 62: 465-503.
Hampsey Laboratory:
Postdoctoral Fellows:


Athar Ansari, PhD
Krishnamurthy Shankarling, PhD
Graduate Students:



Luis Estrella
Sonia Picinich
Mariela Reyes-Reyes
Research Associate:

Terskiy, Alexandra
Undergraduate Student:

Jin Cho