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Transcriptional Regulatory Networks in Saccharomyces cerevisiae
Tong Ihn Lee,1*Nicola J. Rinaldi,12*François Robert,1*Duncan T. Odom,1Ziv Bar-Joseph,3Georg K. Gerber,3Nancy M. Hannett,1Christopher T. Harbison,12Craig M. Thompson,1Itamar Simon,1Julia Zeitlinger,1Ezra G. Jennings,12Heather L. Murray,1D. Benjamin Gordon,1Bing Ren,1John J. Wyrick,1§Jean-Bosco Tagne,1Thomas L. Volkert,1Ernest Fraenkel,1David K. Gifford,3Richard A. Young12
We have determined how most of the transcriptional
regulators encoded in the eukaryote Saccharomyces cerevisiae
associatewith genes across the genome in living cells. Just as maps ofmetabolic networks describe the potential pathways that may beused by
a cell to accomplish metabolic processes, this networkof
regulator-gene interactions describes potential pathways yeastcells
can use to regulate global gene expression programs. Weuse this
information to identify network motifs, the simplestunits of network
architecture, and demonstrate that an automatedprocess can use motifs
to assemble a transcriptional regulatorynetwork structure. Our results
reveal that eukaryotic cellularfunctions are highly connected through
networks of transcriptionalregulators that regulate other
transcriptional regulators.
1 Whitehead Institute for Biomedical Research,
Nine Cambridge Center, Cambridge, MA 02142, USA.
2 Department of Biology, Massachusetts Institute of
Technology, Cambridge, MA 02139, USA.
3 MIT
Laboratory of Computer Science, 200 Technology Square, Cambridge, MA
02139, USA.
*
These authors contributed equally to this work.
Present address: Akceli Inc., 1 Hampshire Street,
Cambridge, MA 02139, USA.
Present address: Ludwig Institute for Cancer
Research, 9500 Gilman Drive, La Jolla, CA 92093, USA.
§
Present address: California Institute of Technology,
Pasadena, CA 91125, USA.
To whom correspondence should be addressed. E-mail:
young{at}wi.mit.edu