Epistatic relationships reveal the functional organization of yeast transcription factors.
The regulation of gene expression is, in large part, mediated by interplay between the general transcription factors (GTFs) that function to bring about the expression of many genes and site-specific DNA-binding transcription factors (STFs). Here, quantitative genetic profiling using the epistatic miniarray profile (E-MAP) approach allowed us to measure 48 391 pairwise genetic interactions, both negative (aggravating) and positive (alleviating), between and among genes encoding STFs and GTFs in Saccharomyces cerevisiae. This allowed us to both reconstruct regulatory models for specific subsets of transcription factors and identify global epistatic patterns. Overall, there was a much stronger preference for negative relative to positive genetic interactions among STFs than there was among GTFs. Negative genetic interactions, which often identify factors working in non-essential, redundant pathways, were also enriched for pairs of STFs that co-regulate similar sets of genes. Microarray analysis demonstrated that pairs of STFs that display negative genetic interactions regulate gene expression in an independent rather than coordinated manner. Collectively, these data suggest that parallel/compensating relationships between regulators, rather than linear pathways, often characterize transcriptional circuits.
Department of Biochemistry and Biophysics, University of California-San Francisco, San Francisco, CA 94143-2542, USA.
Jiashun
J
Zheng
Joris J
JJ
Benschop
Michael
M
Shales
Patrick
P
Kemmeren
Jack
J
Greenblatt
Gerard
G
Cagney
Frank
F
Holstege
Hao
H
Li
Nevan J
NJ
Krogan
D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D004843:Epistasis, Genetic; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000235:genetics / Q000502:physiology*; D053263:Gene Regulatory Networks; D005800:Genes, Fungal; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D014157:Transcription Factors