Open AccessEpistatic relationships reveal the functional organization of yeast transcription factors
Author(s) -
Zheng Jiashun,
Benschop Joris J,
Shales Michael,
Kemmeren Patrick,
Greenblatt Jack,
Cagney Gerard,
Holstege Frank,
Li Hao,
Krogan Nevan J
Publication year - 2010
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2010.77
Subject(s) - biology , genetics , gene , saccharomyces cerevisiae , epistasis , transcription factor , computational biology , transcription (linguistics) , gene expression profiling , gene expression , regulation of gene expression , philosophy , linguistics
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.