TY - JOUR T1 - Establishment of Expression in the SHORTROOT-SCARECROW Transcriptional Cascade through Opposing Activities of Both Activators and Repressors JF - Dev Cell Y1 - 2016 A1 - Sparks, E. E. A1 - Drapek, C. A1 - Gaudinier, A. A1 - Li, S. A1 - Ansariola, M. A1 - Shen, N. A1 - Hennacy, J. H. A1 - Zhang, J. A1 - Turco, G. A1 - Petricka, J. J. A1 - Foret, J. A1 - Hartemink, A. J. A1 - Gordan, R. A1 - Megraw, M. A1 - Brady, S. M. A1 - Benfey, P. N. KW - Arabidopsis Proteins/ genetics/ metabolism KW - Arabidopsis/ genetics/growth & development/ metabolism KW - Computer Simulation KW - Gene Expression Regulation, Plant KW - Gene Regulatory Networks KW - Genes, Plant KW - Genes, Reporter KW - Genes, Synthetic KW - Models, Genetic KW - Plant Roots/cytology/metabolism KW - Plants, Genetically Modified KW - Promoter Regions, Genetic KW - Repressor Proteins/genetics/metabolism KW - Trans-Activators/genetics/metabolism KW - Transcription Factors/ genetics/ metabolism KW - Two-Hybrid System Techniques AB -

Tissue-specific gene expression is often thought to arise from spatially restricted transcriptional cascades. However, it is unclear how expression is established at the top of these cascades in the absence of pre-existing specificity. We generated a transcriptional network to explore how transcription factor expression is established in the Arabidopsis thaliana root ground tissue. Regulators of the SHORTROOT-SCARECROW transcriptional cascade were validated in planta. At the top of this cascade, we identified both activators and repressors of SHORTROOT. The aggregate spatial expression of these regulators is not sufficient to predict transcriptional specificity. Instead, modeling, transcriptional reporters, and synthetic promoters support a mechanism whereby expression at the top of the SHORTROOT-SCARECROW cascade is established through opposing activities of activators and repressors.

VL - 39 SN - 1878-1551 (Electronic)1534-5807 (Linking) UR - https://doi.org/10.1016/j.devcel.2016.09.031 JO - Developmental cell ER - TY - JOUR T1 - Sustained-input switches for transcription factors and microRNAs are central building blocks of eukaryotic gene circuits. JF - Genome Biol Y1 - 2013 A1 - Megraw, Molly A1 - Mukherjee, Sayan A1 - Ohler, Uwe KW - Algorithms KW - Animals KW - Arabidopsis KW - Computational Biology KW - Drosophila melanogaster KW - Gene Expression Regulation KW - Gene Regulatory Networks KW - Humans KW - MicroRNAs KW - Molecular Sequence Annotation KW - Nucleic Acid Conformation KW - Software KW - Transcription Factors AB -

WaRSwap is a randomization algorithm that for the first time provides a practical network motif discovery method for large multi-layer networks, for example those that include transcription factors, microRNAs, and non-regulatory protein coding genes. The algorithm is applicable to systems with tens of thousands of genes, while accounting for critical aspects of biological networks, including self-loops, large hubs, and target rearrangements. We validate WaRSwap on a newly inferred regulatory network from Arabidopsis thaliana, and compare outcomes on published Drosophila and human networks. Specifically, sustained input switches are among the few over-represented circuits across this diverse set of eukaryotes.

VL - 14 IS - 8 ER - TY - JOUR T1 - A stele-enriched gene regulatory network in the Arabidopsis root. JF - Mol Syst Biol Y1 - 2011 A1 - Brady, Siobhan M A1 - Zhang, Lifang A1 - Megraw, Molly A1 - Martinez, Natalia J A1 - Jiang, Eric A1 - Yi, Charles S A1 - Liu, Weilin A1 - Zeng, Anna A1 - Taylor-Teeples, Mallorie A1 - Kim, Dahae A1 - Ahnert, Sebastian A1 - Ohler, Uwe A1 - Ware, Doreen A1 - Walhout, Albertha J M A1 - Benfey, Philip N KW - Arabidopsis KW - Arabidopsis Proteins KW - Gene Expression Profiling KW - Gene Regulatory Networks KW - MicroRNAs KW - Plant Roots KW - Reproducibility of Results KW - Systems Biology KW - Transcription Factors KW - Two-Hybrid System Techniques AB -

Tightly controlled gene expression is a hallmark of multicellular development and is accomplished by transcription factors (TFs) and microRNAs (miRNAs). Although many studies have focused on identifying downstream targets of these molecules, less is known about the factors that regulate their differential expression. We used data from high spatial resolution gene expression experiments and yeast one-hybrid (Y1H) and two-hybrid (Y2H) assays to delineate a subset of interactions occurring within a gene regulatory network (GRN) that determines tissue-specific TF and miRNA expression in plants. We find that upstream TFs are expressed in more diverse cell types than their targets and that promoters that are bound by a relatively large number of TFs correspond to key developmental regulators. The regulatory consequence of many TFs for their target was experimentally determined using genetic analysis. Remarkably, molecular phenotypes were identified for 65% of the TFs, but morphological phenotypes were associated with only 16%. This indicates that the GRN is robust, and that gene expression changes may be canalized or buffered.

VL - 7 ER -