TitleTranscriptional responses to fatty acid are coordinated by combinatorial control.
Publication TypeJournal Article
Year of Publication2007
AuthorsSmith, JJ, Ramsey, SA, Marelli, M, Marzolf, B, Hwang, D, Saleem, RA, Rachubinski, RA, Aitchison, JD
JournalMol Syst Biol
Date Published2007
KeywordsDown-Regulation, Fatty Acids, Gene Expression Regulation, Fungal, Gene Regulatory Networks, Genes, Fungal, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Time Factors, Transcription Factors, Transcription, Genetic

In transcriptional regulatory networks, the coincident binding of a combination of factors to regulate a gene implies the existence of complex mechanisms to control both the gene expression profile and specificity of the response. Unraveling this complexity is a major challenge to biologists. Here, a novel network topology-based clustering approach was applied to condition-specific genome-wide chromatin localization and expression data to characterize a dynamic transcriptional regulatory network responsive to the fatty acid oleate. A network of four (predicted) regulators of the response (Oaf1p, Pip2p, Adr1p and Oaf3p) was investigated. By analyzing trends in the network structure, we found that two groups of multi-input motifs form in response to oleate, each controlling distinct functional classes of genes. This functionality is contributed in part by Oaf1p, which is a component of both types of multi-input motifs and has two different regulatory activities depending on its binding context. The dynamic cooperation between Oaf1p and Pip2p appears to temporally synchronize the two different responses. Together, these data suggest a network mechanism involving dynamic combinatorial control for coordinating transcriptional responses.

Alternate JournalMol Syst Biol
PubMed ID17551510
PubMed Central IDPMC1911199
Grant ListR01 GM067228 / GM / NIGMS NIH HHS / United States
RR022220 / RR / NCRR NIH HHS / United States
U54 RR022220 / RR / NCRR NIH HHS / United States
P50 GM076547 / GM / NIGMS NIH HHS / United States
GM067228 / GM / NIGMS NIH HHS / United States