Reconstruction of a Global Transcriptional Regulatory Network for Control of Lipid Metabolism in Yeast by Using Chromatin Immunoprecipitation with Lambda Exonuclease Digestion
Journal article, 2018

To build transcription regulatory networks, transcription factor binding must be analyzed in cells grown under different conditions because their responses and targets differ depending on environmental conditions. We performed wholegenome analysis of the DNA binding of five Saccharomyces cerevisiae transcription factors involved in lipid metabolism, Ino2, Ino4, Hap1, Oaf1, and Pip2, in response to four different environmental conditions in chemostat cultures, which allowed us to keep the specific growth rate constant. Chromatin immunoprecipitation with lambda exonuclease digestion (ChIP-exo) enabled the detection of binding events at a high resolution. We discovered a large number of unidentified targets and thus expanded functions for each transcription factor (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. Combining the new binding data with previously published data from transcription factor deletion studies revealed the high complexity of the transcriptional regulatory network for lipid metabolism in yeast, which involves the combinatorial and complementary regulation by multiple transcription factors. We anticipate that our work will provide insights into transcription factor binding dynamics that will prove useful for the understanding of transcription regulatory networks.

lipid metabolic map

novel targets

environmental response

ChIP-exo

transcriptional regulatory network

Author

David Bergenholm

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Guodong Liu

Shandong University

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Petter Holland

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Jens B Nielsen

Technical University of Denmark (DTU)

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

mSystems

2379-5077 (ISSN)

Vol. 3 4 e00215-17

Subject Categories

Cell Biology

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Bioinformatics and Systems Biology

Infrastructure

C3SE (Chalmers Centre for Computational Science and Engineering)

DOI

10.1128/mSystems.00215-17

More information

Latest update

1/14/2020