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 and Gloria M. Coruzzi ()
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Matthew D. Brooks: New York University
Jacopo Cirrone: New York University
Angelo V. Pasquino: New York University
Jose M. Alvarez: New York University
Joseph Swift: New York University
Shipra Mittal: New York University
Che-Lun Juang: New York University
Kranthi Varala: Purdue University
Rodrigo A. Gutiérrez: Pontificia Universidad Católica de Chile
Gabriel Krouk: Montpellier SupAgro
Dennis Shasha: New York University
Gloria M. Coruzzi: New York University

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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 TF1-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 TF2 targets, which in turn regulate 76% and 87% of TF1 indirect targets in planta, respectively. These results have implications for N-use and the approach can reveal temporal networks for any biological system.

Date: 2019
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DOI: 10.1038/s41467-019-09522-1

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