Network Walking charts transcriptional dynamics of nitrogen signaling by integrating validated and predicted genome-wide interactions

Matthew D. Brooks, Jacopo Cirrone, Angelo V. Pasquino, Jose M. Alvarez, Joseph Swift, Shipra Mittal, Che Lun Juang, Kranthi Varala, Rodrigo A. Gutiérrez, Gabriel Krouk, Dennis Shasha, Gloria M. Coruzzi

Research output: Contribution to journalArticle

Abstract

Charting a temporal path in gene networks requires linking early transcription factor (TF)-triggered events to downstream effects. We scale-up a cell-based TF-perturbation assay to identify direct regulated targets of 33 nitrogen (N)-early response TFs encompassing 88% of N-responsive Arabidopsis genes. We uncover a duality where each TF is an inducer and repressor, and in vitro cis-motifs are typically specific to regulation directionality. Validated TF-targets (71,836) are used to refine precision of a time-inferred root network, connecting 145 N-responsive TFs and 311 targets. These data are used to chart network paths from direct TF 1 -regulated targets identified in cells to indirect targets responding only in planta via Network Walking. We uncover network paths from TGA1 and CRF4 to direct TF 2 targets, which in turn regulate 76% and 87% of TF 1 indirect targets in planta, respectively. These results have implications for N-use and the approach can reveal temporal networks for any biological system.

Original languageEnglish (US)
Article number1569
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Brooks, M. D., Cirrone, J., Pasquino, A. V., Alvarez, J. M., Swift, J., Mittal, S., Juang, C. L., Varala, K., Gutiérrez, R. A., Krouk, G., Shasha, D., & Coruzzi, G. M. (2019). Network Walking charts transcriptional dynamics of nitrogen signaling by integrating validated and predicted genome-wide interactions. Nature communications, 10(1), [1569]. https://doi.org/10.1038/s41467-019-09522-1