@article {742, title = {Establishment of Expression in the SHORTROOT-SCARECROW Transcriptional Cascade through Opposing Activities of Both Activators and Repressors}, journal = {Dev Cell}, volume = {39}, year = {2016}, month = {12/2016}, pages = {585-596}, abstract = {

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.

}, keywords = {Arabidopsis Proteins/ genetics/ metabolism, Arabidopsis/ genetics/growth \& development/ metabolism, Computer Simulation, Gene Expression Regulation, Plant, Gene Regulatory Networks, Genes, Plant, Genes, Reporter, Genes, Synthetic, Models, Genetic, Plant Roots/cytology/metabolism, Plants, Genetically Modified, Promoter Regions, Genetic, Repressor Proteins/genetics/metabolism, Trans-Activators/genetics/metabolism, Transcription Factors/ genetics/ metabolism, Two-Hybrid System Techniques}, isbn = {1878-1551 (Electronic)1534-5807 (Linking)}, url = {https://doi.org/10.1016/j.devcel.2016.09.031}, author = {Sparks, E. E. and Drapek, C. and Gaudinier, A. and Li, S. and Ansariola, M. and Shen, N. and Hennacy, J. H. and Zhang, J. and Turco, G. and Petricka, J. J. and Foret, J. and Hartemink, A. J. and Gordan, R. and Megraw, M. and Brady, S. M. and Benfey, P. N.} } @article {316, title = {The cyclophilin A DIAGEOTROPICA gene affects auxin transport in both root and shoot to control lateral root formation.}, journal = {Development}, volume = {142}, year = {2015}, month = {2015 Feb 15}, pages = {712-21}, abstract = {

Cyclophilin A is a conserved peptidyl-prolyl cis-trans isomerase (PPIase) best known as the cellular receptor of the immunosuppressant cyclosporine A. Despite significant effort, evidence of developmental functions of cyclophilin A in non-plant systems has remained obscure. Mutations in a tomato (Solanum lycopersicum) cyclophilin A ortholog, DIAGEOTROPICA (DGT), have been shown to abolish the organogenesis of lateral roots; however, a mechanistic explanation of the phenotype is lacking. Here, we show that the dgt mutant lacks auxin maxima relevant to priming and specification of lateral root founder cells. DGT is expressed in shoot and root, and localizes to both the nucleus and cytoplasm during lateral root organogenesis. Mutation of ENTIRE/IAA9, a member of the auxin-responsive Aux/IAA protein family of transcriptional repressors, partially restores the inability of dgt to initiate lateral root primordia but not the primordia outgrowth. By comparison, grafting of a wild-type scion restores the process of lateral root formation, consistent with participation of a mobile signal. Antibodies do not detect movement of the DGT protein into the dgt rootstock; however, experiments with radiolabeled auxin and an auxin-specific microelectrode demonstrate abnormal auxin fluxes. Functional studies of DGT in heterologous yeast and tobacco-leaf auxin-transport systems demonstrate that DGT negatively regulates PIN-FORMED (PIN) auxin efflux transporters by affecting their plasma membrane localization. Studies in tomato support complex effects of the dgt mutation on PIN expression level, expression domain and plasma membrane localization. Our data demonstrate that DGT regulates auxin transport in lateral root formation.

}, keywords = {Arabidopsis, Biological Transport, Cyclophilin A, Indoleacetic Acids, Lycopersicon esculentum, Plant Proteins, Plant Roots, Plant Shoots}, issn = {1477-9129}, doi = {10.1242/dev.113225}, author = {Ivanchenko, Maria G and Zhu, Jinsheng and Wang, Bangjun and Medveck{\'a}, Eva and Du, Yunlong and Azzarello, Elisa and Mancuso, Stefano and Megraw, Molly and Filichkin, Sergei and Dubrovsky, Joseph G and Friml, Ji{\v r}{\'\i} and Geisler, Markus} } @article {322, title = {A stele-enriched gene regulatory network in the Arabidopsis root.}, journal = {Mol Syst Biol}, volume = {7}, year = {2011}, month = {2011 Jan 18}, pages = {459}, abstract = {

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.

}, keywords = {Arabidopsis, Arabidopsis Proteins, Gene Expression Profiling, Gene Regulatory Networks, MicroRNAs, Plant Roots, Reproducibility of Results, Systems Biology, Transcription Factors, Two-Hybrid System Techniques}, issn = {1744-4292}, doi = {10.1038/msb.2010.114}, author = {Brady, Siobhan M and Zhang, Lifang and Megraw, Molly and Martinez, Natalia J and Jiang, Eric and Yi, Charles S and Liu, Weilin and Zeng, Anna and Taylor-Teeples, Mallorie and Kim, Dahae and Ahnert, Sebastian and Ohler, Uwe and Ware, Doreen and Walhout, Albertha J M and Benfey, Philip N} } @article {328, title = {Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer.}, journal = {Proc Natl Acad Sci U S A}, volume = {105}, year = {2008}, month = {2008 May 13}, pages = {7004-9}, abstract = {

MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs that function as negative gene regulators. miRNA deregulation is involved in the initiation and progression of human cancer; however, the underlying mechanism and its contributions to genome-wide transcriptional changes in cancer are still largely unknown. We studied miRNA deregulation in human epithelial ovarian cancer by integrative genomic approach, including miRNA microarray (n = 106), array-based comparative genomic hybridization (n = 109), cDNA microarray (n = 76), and tissue array (n = 504). miRNA expression is markedly down-regulated in malignant transformation and tumor progression. Genomic copy number loss and epigenetic silencing, respectively, may account for the down-regulation of approximately 15\% and at least approximately 36\% of miRNAs in advanced ovarian tumors and miRNA down-regulation contributes to a genome-wide transcriptional deregulation. Last, eight miRNAs located in the chromosome 14 miRNA cluster (Dlk1-Gtl2 domain) were identified as potential tumor suppressor genes. Therefore, our results suggest that miRNAs may offer new biomarkers and therapeutic targets in epithelial ovarian cancer.

}, keywords = {DNA, Neoplasm, Down-Regulation, Epigenesis, Genetic, Epithelial Cells, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genome, Human, Humans, MicroRNAs, Neoplasm Staging, Ovarian Neoplasms, Ribonuclease III, RNA, Messenger, Survival Analysis}, issn = {1091-6490}, doi = {10.1073/pnas.0801615105}, author = {Zhang, Lin and Volinia, Stefano and Bonome, Tomas and Calin, George Adrian and Greshock, Joel and Yang, Nuo and Liu, Chang-Gong and Giannakakis, Antonis and Alexiou, Pangiotis and Hasegawa, Kosei and Johnstone, Cameron N and Megraw, Molly S and Adams, Sarah and Lassus, Heini and Huang, Jia and Kaur, Sippy and Liang, Shun and Sethupathy, Praveen and Leminen, Arto and Simossis, Victor A and Sandaltzopoulos, Raphael and Naomoto, Yoshio and Katsaros, Dionyssios and Gimotty, Phyllis A and DeMichele, Angela and Huang, Qihong and B{\"u}tzow, Ralf and Rustgi, Anil K and Weber, Barbara L and Birrer, Michael J and Hatzigeorgiou, Artemis G and Croce, Carlo M and Coukos, George} } @article {332, title = {microRNAs exhibit high frequency genomic alterations in human cancer.}, journal = {Proc Natl Acad Sci U S A}, volume = {103}, year = {2006}, month = {2006 Jun 13}, pages = {9136-41}, abstract = {

MicroRNAs (miRNAs) are endogenous noncoding RNAs, which negatively regulate gene expression. To determine genomewide miRNA DNA copy number abnormalities in cancer, 283 known human miRNA genes were analyzed by high-resolution array-based comparative genomic hybridization in 227 human ovarian cancer, breast cancer, and melanoma specimens. A high proportion of genomic loci containing miRNA genes exhibited DNA copy number alterations in ovarian cancer (37.1\%), breast cancer (72.8\%), and melanoma (85.9\%), where copy number alterations observed in \>15\% tumors were considered significant for each miRNA gene. We identified 41 miRNA genes with gene copy number changes that were shared among the three cancer types (26 with gains and 15 with losses) as well as miRNA genes with copy number changes that were unique to each tumor type. Importantly, we show that miRNA copy changes correlate with miRNA expression. Finally, we identified high frequency copy number abnormalities of Dicer1, Argonaute2, and other miRNA-associated genes in breast and ovarian cancer as well as melanoma. These findings support the notion that copy number alterations of miRNAs and their regulatory genes are highly prevalent in cancer and may account partly for the frequent miRNA gene deregulation reported in several tumor types.

}, keywords = {Breast Neoplasms, Female, Gene Dosage, Gene Expression Profiling, Humans, MicroRNAs, Neoplasms, Nucleic Acid Hybridization, Oligonucleotide Array Sequence Analysis, Ovarian Neoplasms, Statistics as Topic}, issn = {0027-8424}, doi = {10.1073/pnas.0508889103}, author = {Zhang, Lin and Huang, Jia and Yang, Nuo and Greshock, Joel and Megraw, Molly S and Giannakakis, Antonis and Liang, Shun and Naylor, Tara L and Barchetti, Andrea and Ward, Michelle R and Yao, George and Medina, Angelica and O{\textquoteright}brien-Jenkins, Ann and Katsaros, Dionyssios and Hatzigeorgiou, Artemis and Gimotty, Phyllis A and Weber, Barbara L and Coukos, George} }