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

ABSTRACT 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 whole-genome analysis of the DNA binding of five Saccharomyces c...

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Autores principales: David Bergenholm, Guodong Liu, Petter Holland, Jens Nielsen
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Publicado: American Society for Microbiology 2018
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spelling oai:doaj.org-article:b3b0bc78d88f4d9d9f00106bdcdb04ff2021-12-02T19:45:30ZReconstruction of a Global Transcriptional Regulatory Network for Control of Lipid Metabolism in Yeast by Using Chromatin Immunoprecipitation with Lambda Exonuclease Digestion10.1128/mSystems.00215-172379-5077https://doaj.org/article/b3b0bc78d88f4d9d9f00106bdcdb04ff2018-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00215-17https://doaj.org/toc/2379-5077ABSTRACT 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 whole-genome 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. IMPORTANCE Transcription factors play a crucial role in the regulation of gene expression and adaptation to different environments. To better understand the underlying roles of these adaptations, we performed experiments that give us high-resolution binding of transcription factors to their targets. We investigated five transcription factors involved in lipid metabolism in yeast, and we discovered multiple novel targets and condition-specific responses that allow us to draw a better regulatory map of the lipid metabolism.David BergenholmGuodong LiuPetter HollandJens NielsenAmerican Society for MicrobiologyarticleChIP-exotranscriptional regulatory networkenvironmental responselipid metabolic mapnovel targetsMicrobiologyQR1-502ENmSystems, Vol 3, Iss 4 (2018)
institution DOAJ
collection DOAJ
language EN
topic ChIP-exo
transcriptional regulatory network
environmental response
lipid metabolic map
novel targets
Microbiology
QR1-502
spellingShingle ChIP-exo
transcriptional regulatory network
environmental response
lipid metabolic map
novel targets
Microbiology
QR1-502
David Bergenholm
Guodong Liu
Petter Holland
Jens Nielsen
Reconstruction of a Global Transcriptional Regulatory Network for Control of Lipid Metabolism in Yeast by Using Chromatin Immunoprecipitation with Lambda Exonuclease Digestion
description ABSTRACT 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 whole-genome 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. IMPORTANCE Transcription factors play a crucial role in the regulation of gene expression and adaptation to different environments. To better understand the underlying roles of these adaptations, we performed experiments that give us high-resolution binding of transcription factors to their targets. We investigated five transcription factors involved in lipid metabolism in yeast, and we discovered multiple novel targets and condition-specific responses that allow us to draw a better regulatory map of the lipid metabolism.
format article
author David Bergenholm
Guodong Liu
Petter Holland
Jens Nielsen
author_facet David Bergenholm
Guodong Liu
Petter Holland
Jens Nielsen
author_sort David Bergenholm
title Reconstruction of a Global Transcriptional Regulatory Network for Control of Lipid Metabolism in Yeast by Using Chromatin Immunoprecipitation with Lambda Exonuclease Digestion
title_short Reconstruction of a Global Transcriptional Regulatory Network for Control of Lipid Metabolism in Yeast by Using Chromatin Immunoprecipitation with Lambda Exonuclease Digestion
title_full Reconstruction of a Global Transcriptional Regulatory Network for Control of Lipid Metabolism in Yeast by Using Chromatin Immunoprecipitation with Lambda Exonuclease Digestion
title_fullStr Reconstruction of a Global Transcriptional Regulatory Network for Control of Lipid Metabolism in Yeast by Using Chromatin Immunoprecipitation with Lambda Exonuclease Digestion
title_full_unstemmed Reconstruction of a Global Transcriptional Regulatory Network for Control of Lipid Metabolism in Yeast by Using Chromatin Immunoprecipitation with Lambda Exonuclease Digestion
title_sort reconstruction of a global transcriptional regulatory network for control of lipid metabolism in yeast by using chromatin immunoprecipitation with lambda exonuclease digestion
publisher American Society for Microbiology
publishDate 2018
url https://doaj.org/article/b3b0bc78d88f4d9d9f00106bdcdb04ff
work_keys_str_mv AT davidbergenholm reconstructionofaglobaltranscriptionalregulatorynetworkforcontroloflipidmetabolisminyeastbyusingchromatinimmunoprecipitationwithlambdaexonucleasedigestion
AT guodongliu reconstructionofaglobaltranscriptionalregulatorynetworkforcontroloflipidmetabolisminyeastbyusingchromatinimmunoprecipitationwithlambdaexonucleasedigestion
AT petterholland reconstructionofaglobaltranscriptionalregulatorynetworkforcontroloflipidmetabolisminyeastbyusingchromatinimmunoprecipitationwithlambdaexonucleasedigestion
AT jensnielsen reconstructionofaglobaltranscriptionalregulatorynetworkforcontroloflipidmetabolisminyeastbyusingchromatinimmunoprecipitationwithlambdaexonucleasedigestion
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