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

Författare

David Bergenholm

Chalmers, Biologi och bioteknik, Systembiologi

Guodong Liu

Shandong University

Chalmers, Biologi och bioteknik, Systembiologi

Petter Holland

Chalmers, Biologi och bioteknik, Systembiologi

Jens B Nielsen

Danmarks Tekniske Universitet (DTU)

Chalmers, Biologi och bioteknik, Systembiologi

mSystems

2379-5077 (ISSN)

Vol. 3 4 e00215-17

Ämneskategorier

Cellbiologi

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

Bioinformatik och systembiologi

Infrastruktur

C3SE (Chalmers Centre for Computational Science and Engineering)

DOI

10.1128/mSystems.00215-17

Mer information

Senast uppdaterat

2020-01-14