Reconstruction of a Global Transcriptional Regulatory Network for Control of Lipid Metabolism in Yeast by Using Chromatin Immunoprecipitation with Lambda Exonuclease Digestion

We performed whole genome analysis of the DNA binding of five Saccharomyces cerevisiae transcription factors involved in lipid biosynthesis, Ino2, Ino4, Hap1, Oaf1 and Pip2, in response to four different environmental conditions. Using chromatin immunoprecipitation with lambda exonuclease digestion (ChIP-exo) we discovered a large number of so-far unidentified targets with nucleotide resolution. Based on the newly identified targets we document expanded functions for all five transcription factors, e.g. glutamate biosynthesis as a target of Oaf1 and Pip2. Moreover, condition-dependent binding of transcription factors in response to cell metabolic state, e.g. differential binding of Ino2 between fermentative and respiratory metabolic conditions was clearly suggested. Using our data we build a comprehensive transcriptional regulatory network for lipid metabolism in yeast. The binding sites of Ino2, Ino4, Hap1, Oaf1 and Pip2 when cells were grown in Glucose-limited, Nitrogen-limited, Ethanol-limited or Oxygen/Glucose-limited chemostat cultivations were measured in biological duplicates