@article {750, title = {Arabidopsis bioinformatics resources: The current state, challenges, and priorities for the future}, journal = {Plant Direct}, volume = {3}, year = {2019}, month = {01/2019}, url = {https://onlinelibrary.wiley.com/doi/full/10.1002/pld3.109}, author = {Colleen Doherty and Joanna Friesner and Brian Gregory and Ann Loraine and Molly Megraw and Nicholas Provart and R Keith Slotkin and Chris Town and Sarah M Assmann and Michael Axtell and Tanya Berardini and Sixue Chen and Malia Gehan and Eva Huala and Pankaj Jaiswal and Stephen Larson and Song Li and Sean May and Todd Michael and Chris Pires and Chris Topp and Justin Walley and Eve Wurtele} } @article {315, title = {Environmental stresses modulate abundance and timing of alternatively spliced circadian transcripts in Arabidopsis.}, journal = {Mol Plant}, volume = {8}, year = {2015}, month = {2015 Feb}, pages = {207-27}, abstract = {

Environmental stresses profoundly altered accumulation of nonsense mRNAs including intron-retaining (IR) transcripts in Arabidopsis. Temporal patterns of stress-induced IR mRNAs were dissected using both oscillating and non-oscillating transcripts. Broad-range thermal cycles triggered a sharp increase in the long IR CCA1 isoforms and altered their phasing to different times of day. Both abiotic and biotic stresses such as drought or Pseudomonas syringae infection induced a similar increase. Thermal stress induced a time delay in accumulation of CCA1 I4Rb transcripts, whereas functional mRNA showed steady oscillations. Our data favor a hypothesis that stress-induced instabilities of the central oscillator can be in part compensated through fluctuations in abundance and out-of-phase oscillations of CCA1 IR transcripts. Taken together, our results support a concept that mRNA abundance can be modulated through altering ratios between functional and nonsense/IR transcripts. SR45 protein specifically bound to the retained CCA1 intron in\ vitro, suggesting that this splicing factor could be involved in regulation of intron retention. Transcriptomes of nonsense-mediated mRNA decay (NMD)-impaired and heat-stressed plants shared a set of retained introns associated with stress- and defense-inducible transcripts. Constitutive activation of certain stress response networks in an NMD mutant could be linked to disequilibrium between functional and nonsense mRNAs.

}, keywords = {Alternative Splicing, Arabidopsis, Arabidopsis Proteins, Circadian Clocks, Gene Expression Regulation, Plant, Introns, Nonsense Mediated mRNA Decay}, issn = {1752-9867}, doi = {10.1016/j.molp.2014.10.011}, author = {Filichkin, Sergei A and Cumbie, Jason S and Dharmawardhana, Palitha and Jaiswal, Pankaj and Chang, Jeff H and Palusa, Saiprasad G and Reddy, A S N and Megraw, Molly and Mockler, Todd C} } @article {317, title = {Environmental Stresses Modulate Abundance and Timing of Alternatively Spliced Circadian Transcripts in Arabidopsis.}, journal = {Mol Plant}, year = {2014}, month = {2014 Nov 3}, abstract = {

Environmental stresses profoundly altered accumulation of nonsense mRNAs including intron retaining (IR) transcripts in Arabidopsis. Temporal patterns of stress-induced IR mRNAs were dissected using both oscillating and non-oscillating transcripts. Broad range thermal cycles triggered a sharp increase in the long intron retaining CCA1 isoforms and altered their phasing to different times of day. Both abiotic and biotic stresses such as drought or P. syringae infection induced similar increase. Thermal stress induced a time delay in accumulation of CCA1 I4Rb transcripts whereas functional mRNA showed steady oscillations. Our data favor a hypothesis that stress-induced instabilities of the central oscillator can be in part compensated through fluctuations in abundance and out of phase oscillations of CCA1 IR transcripts. Altogether, our results support a concept that mRNA abundance can be modulated through altering ratios between functional and nonsense/IR transcripts. SR45 protein specifically bound to the retained CCA1 intron in vitro, suggesting that this splicing factor could be involved in regulation of intron retention. Transcriptomes of NMD-impaired and heat-stressed plants shared a set of retained introns associated with stress- and defense-inducible transcripts. Constitutive activation of certain stress response networks in an NMD mutant could be linked to disequilibrium between functional and nonsense mRNAs.

}, issn = {1752-9867}, doi = {10.1093/mp/ssu130}, author = {Filichkin, Sergei A and Cumbie, Jason S and Dharmawadhana, J Palitha and Jaiswal, Pankaj and Chang, Jeff H and Palusa, Saiprasad G and Reddy, A S N and Megraw, Molly and Mockler, Todd C} } @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 {326, title = {A transcription factor affinity-based code for mammalian transcription initiation.}, journal = {Genome Res}, volume = {19}, year = {2009}, month = {2009 Apr}, pages = {644-56}, abstract = {

The recent arrival of large-scale cap analysis of gene expression (CAGE) data sets in mammals provides a wealth of quantitative information on coding and noncoding RNA polymerase II transcription start sites (TSS). Genome-wide CAGE studies reveal that a large fraction of TSS exhibit peaks where the vast majority of associated tags map to a particular location ( approximately 45\%), whereas other active regions contain a broader distribution of initiation events. The presence of a strong single peak suggests that transcription at these locations may be mediated by position-specific sequence features. We therefore propose a new model for single-peaked TSS based solely on known transcription factors (TFs) and their respective regions of positional enrichment. This probabilistic model leads to near-perfect classification results in cross-validation (auROC = 0.98), and performance in genomic scans demonstrates that TSS prediction with both high accuracy and spatial resolution is achievable for a specific but large subgroup of mammalian promoters. The interpretable model structure suggests a DNA code in which canonical sequence features such as TATA-box, Initiator, and GC content do play a significant role, but many additional TFs show distinct spatial biases with respect to TSS location and are important contributors to the accurate prediction of single-peak transcription initiation sites. The model structure also reveals that CAGE tag clusters distal from annotated gene starts have distinct characteristics compared to those close to gene 5\&$\#$39;-ends. Using this high-resolution single-peak model, we predict TSS for approximately 70\% of mammalian microRNAs based on currently available data.

[Links to Tools and Supplementary Materials]

}, keywords = {Base Composition, Databases, Genetic, DNA, Gene Expression Regulation, Genome, Human, Humans, Promoter Regions, Genetic, RNA Polymerase II, TATA Box, Transcription Factors, Transcription Initiation Site, Transcription, Genetic}, issn = {1088-9051}, doi = {10.1101/gr.085449.108}, author = {Megraw, Molly and Pereira, Fernando and Jensen, Shane T and Ohler, Uwe and Hatzigeorgiou, Artemis G} } @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 {331, title = {MicroRNA promoter element discovery in Arabidopsis.}, journal = {RNA}, volume = {12}, year = {2006}, month = {2006 Sep}, pages = {1612-9}, abstract = {

In this study we present a method of identifying Arabidopsis miRNA promoter elements using known transcription factor binding motifs. We provide a comparative analysis of the representation of these elements in miRNA promoters, protein-coding gene promoters, and random genomic sequences. We report five transcription factor (TF) binding motifs that show evidence of overrepresentation in miRNA promoter regions relative to the promoter regions of protein-coding genes. This investigation is based on the analysis of 800-nucleotide regions upstream of 63 experimentally verified Transcription Start Sites (TSS) for miRNA primary transcripts in Arabidopsis. While the TATA-box binding motif was also previously reported by Xie and colleagues, the transcription factors AtMYC2, ARF, SORLREP3, and LFY are identified for the first time as overrepresented binding motifs in miRNA promoters.

}, keywords = {Arabidopsis, Base Sequence, Binding Sites, Databases, Genetic, Feedback, Physiological, Genes, Plant, MicroRNAs, Promoter Regions, Genetic, TATA Box, Transcription Factors, Transcription Initiation Site}, issn = {1355-8382}, doi = {10.1261/rna.130506}, author = {Megraw, Molly and Baev, Vesselin and Rusinov, Ventsislav and Jensen, Shane T and Kalantidis, Kriton and Hatzigeorgiou, Artemis G} }