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

Matthew D Brooks (1) , Jacopo Cirrone (2) , Angelo V Pasquino (1) , José M Alvarez (3) , Joseph Swift (1) , Shipra Mittal (1) , Che-Lun Juang (1) , Kranthi Varala (4) , Rodrigo A Gutiérrez (5) , Gabriel Krouk (6, 6) , Dennis Shasha (2) , Gloria M Coruzzi (1)

1 Center for Genomics and Systems Biology
2 CIMS - Courant Institute of Mathematical Sciences [New York]
3 UNAB - Universidad Andrés Bello [Santiago]
4 Purdue University [West Lafayette]
5 FONDAP - Departamento de Genética Molecular y Microbiología
6 BPMP - Biochimie et Physiologie Moléculaire des Plantes

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.

Domaines: Botanique; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Matthew D Brooks, Jacopo Cirrone, Angelo V Pasquino, José M Alvarez, Joseph Swift, et al.. Network Walking charts transcriptional dynamics of nitrogen signaling by integrating validated and predicted genome-wide interactions. Nature Communications, 2019, 10, pp.1569. ⟨10.1038/s41467-019-09522-1⟩. ⟨hal-02122905⟩