Predictive models of eukaryotic transcriptional regulation reveals changes in transcription factor roles and promoter usage between metabolic conditions
Artikel i vetenskaplig tidskrift, 2019

Transcription factors (TF) are central to transcriptional regulation, but they are often studied in relative isolation and without close control of the metabolic state of the cell. Here, we describe genome-wide binding (by ChIP-exo) of 15 yeast TFs in four chemostat conditions that cover a range of metabolic states. We integrate this data with transcriptomics and six additional recently mapped TFs to identify predictive models describing how TFs control gene expression in different metabolic conditions. Contributions by TFs to gene regulation are predicted to be mostly activating, additive and well approximated by assuming linear effects from TF binding signal. Notably, using TF binding peaks from peak finding algorithms gave distinctly worse predictions than simply summing the low-noise and high-resolution TF ChIP-exo reads on promoters. Finally, we discover indications of a novel functional role for three TFs; Gcn4, Ert1 and Sut1 during nitrogen limited aerobic fermentation. In only this condition, the three TFs have correlated binding to a large number of genes (enriched for glycolytic and translation processes) and a negative correlation to target gene transcript levels.

Författare

Petter Holland

Chalmers, Biologi och bioteknik, Systembiologi

David Bergenholm

Chalmers, Biologi och bioteknik, Systembiologi

Christoph Sebastian Börlin

Chalmers, Biologi och bioteknik, Systembiologi

Guodong Liu

Chalmers, Biologi och bioteknik, Systembiologi

Jens B Nielsen

Novo Nordisk Fonden

Chalmers, Biologi och bioteknik, Systembiologi

Danmarks Tekniske Universitet (DTU)

Nucleic Acids Research

0305-1048 (ISSN) 1362-4962 (eISSN)

Vol. 47 10 4986-5000

Ämneskategorier

Mikrobiologi

Bioinformatik och systembiologi

Genetik

DOI

10.1093/nar/gkz253

PubMed

30976803

Mer information

Senast uppdaterat

2019-07-16