The C. elegans genome contains ~20,000 protein-coding genes and many
non-coding RNA genes, including more than 100 microRNAs. Most of these genes
are differentially expressed; i.e. at different times and in different cells.
As a result, each cell/tissue/organ expresses a different subset of the total
transcriptome. Differential gene expression is governed by regulatory
transcription factors (TFs) that bind to cis-regulatory elements located in
their target genes.
In addition, gene expression can be regulated through the action of microRNAs
that inhibit mRNA stability and/or translation.
We predict that ~934 of the ~20,000 worm genes encode TFs (Reece-Hoyes et al, 2005).
To gain insight into C. elegans differential gene expression at a systems level,
we systematically identify protein-DNA interactions (PDIs) between TFs and their
target genes. To do so, we have developed a Gateway-compatible yeast one-hybrid (Y1H)
system (Deplancke et al, 2004).
This Y1H system is compatible with the C. elegans
promoterome (Dupuy et al, 2004)
for the creation of DNA baits, and the ORFeome for
the creation of TF resources (i.e. Y1H “preys”). Using the Y1H system we have found several novel putative TFs (Deplancke et al, 2006). We are also mapping protein-protein
interactions (PPIs) between TFs to identify TF homo- and heterodimers. To do so we
employ high-throughput yeast two-hybrid (Y2H) assays. Finally, we are determining
where TFs and their targets are expressed and how target expression is affected in the absence of a regulating TF. To do so, we fuse promoters to the green
fluorescent protein (GFP) and examine GFP expression in living animals.
This localization of expression mapping project is a collaboration between our
laboratory and the groups of Marc Vidal (Dana-Farber Center for Cancer Systems Biology)
and Ian Hope (University of Leeds, UK).
PDI, PPI and gene expression data generated by the Walhout laboratory and by other laboratories are
collected and made available to the community through EDGEdb
(elegans differential gene expression database). We encourage the C. elegans community to send us their PDI and TF dimerization PPI data to keep the database current. For more information on
C. elegans genes and biology, please visit WormBase. For more information on
the worm PPI interactome, the ORFeome and Promoterome, please visit the Vidal lab
website. For more information regarding gene expression patterns, please
visit the Hope lab website. For more information about the Walhout laboratory,
please visit the lab website.
Contact information:
A.J. Marian Walhout
Program in Gene Function and Expression
Program in Molecular Medicine
University of Massachusetts Medical School
364 Plantation Street
Lazare Research Building, Room 605
Worcester, MA 01605
Phone: 508-856-4364
Email: marian.walhout@umassmed.edu
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