• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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.

Pubmed ID: 20959818

Authors

  • Zheng J
  • Benschop JJ
  • Shales M
  • Kemmeren P
  • Greenblatt J
  • Cagney G
  • Holstege F
  • Li H
  • Krogan NJ

Journal

Molecular systems biology

Publication Data

October 5, 2010

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM081879
  • Agency: NIGMS NIH HHS, Id: GM084279
  • Agency: NIGMS NIH HHS, Id: GM084448
  • Agency: NIGMS NIH HHS, Id: GM70808
  • Agency: NIGMS NIH HHS, Id: GM90293
  • Agency: NIGMS NIH HHS, Id: P50 GM081879
  • Agency: NIGMS NIH HHS, Id: R01 GM084448

Mesh Terms

  • Cluster Analysis
  • Computational Biology
  • Epistasis, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal
  • Gene Regulatory Networks
  • Genes, Fungal
  • Models, Genetic
  • Oligonucleotide Array Sequence Analysis
  • Saccharomyces cerevisiae
  • Transcription Factors