02389nas a2200433 4500008004100000022001400041245007000055210006600125260001600191300000800207490000600215520115000221653001601371653002501387653003001412653002901442653001401471653001601485653003101501653002001532653002601552653003301578100002201611700001801633700001801651700002501669700001601694700001901710700001601729700001501745700002901760700001501789700002201804700001501826700001701841700002701858700002201885856004801907 2011 eng d a1744-429200aA stele-enriched gene regulatory network in the Arabidopsis root.0 asteleenriched gene regulatory network in the Arabidopsis root c2011 Jan 18 a4590 v73 a
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.
10aArabidopsis10aArabidopsis Proteins10aGene Expression Profiling10aGene Regulatory Networks10aMicroRNAs10aPlant Roots10aReproducibility of Results10aSystems Biology10aTranscription Factors10aTwo-Hybrid System Techniques1 aBrady, Siobhan, M1 aZhang, Lifang1 aMegraw, Molly1 aMartinez, Natalia, J1 aJiang, Eric1 aYi, Charles, S1 aLiu, Weilin1 aZeng, Anna1 aTaylor-Teeples, Mallorie1 aKim, Dahae1 aAhnert, Sebastian1 aOhler, Uwe1 aWare, Doreen1 aWalhout, Albertha, J M1 aBenfey, Philip, N uhttp://megraw.cgrb.oregonstate.edu/node/32203230nas a2200709 4500008004100000022001400041245010600055210006900161260001600230300001100246490000800257520120600265653001801471653002001489653002401509653002101533653001101554653003001565653004301595653001801638653001101656653001401667653002101681653002201702653002101724653001901745653002201764100001501786700002101801700001801822700002601840700001901866700001401885700002001899700002501919700002301944700002001967700002601987700002102013700001702034700001802051700001502069700001602084700001602100700002402116700001802140700002402158700002902182700002002211700002502231700002402256700002202280700001802302700001802320700002002338700002202358700002302380700003002403700002002433700001902453856004802472 2008 eng d a1091-649000aGenomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer.0 aGenomic and epigenetic alterations deregulate microRNA expressio c2008 May 13 a7004-90 v1053 aMicroRNAs (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.
10aDNA, Neoplasm10aDown-Regulation10aEpigenesis, Genetic10aEpithelial Cells10aFemale10aGene Expression Profiling10aGene Expression Regulation, Neoplastic10aGenome, Human10aHumans10aMicroRNAs10aNeoplasm Staging10aOvarian Neoplasms10aRibonuclease III10aRNA, Messenger10aSurvival Analysis1 aZhang, Lin1 aVolinia, Stefano1 aBonome, Tomas1 aCalin, George, Adrian1 aGreshock, Joel1 aYang, Nuo1 aLiu, Chang-Gong1 aGiannakakis, Antonis1 aAlexiou, Pangiotis1 aHasegawa, Kosei1 aJohnstone, Cameron, N1 aMegraw, Molly, S1 aAdams, Sarah1 aLassus, Heini1 aHuang, Jia1 aKaur, Sippy1 aLiang, Shun1 aSethupathy, Praveen1 aLeminen, Arto1 aSimossis, Victor, A1 aSandaltzopoulos, Raphael1 aNaomoto, Yoshio1 aKatsaros, Dionyssios1 aGimotty, Phyllis, A1 aDeMichele, Angela1 aHuang, Qihong1 aBützow, Ralf1 aRustgi, Anil, K1 aWeber, Barbara, L1 aBirrer, Michael, J1 aHatzigeorgiou, Artemis, G1 aCroce, Carlo, M1 aCoukos, George uhttp://megraw.cgrb.oregonstate.edu/node/32802694nas a2200481 4500008004100000022001400041245007400055210006900129260001600198300001200214490000800226520132400234653002101558653001101579653001601590653003001606653001101636653001401647653001401661653003101675653004401706653002201750653002401772100001501796700001501811700001401826700001901840700002101859700002501880700001601905700002001921700002201941700002201963700001601985700002102001700002502022700002502047700002702072700002402099700002202123700001902145856004802164 2006 eng d a0027-842400amicroRNAs exhibit high frequency genomic alterations in human cancer.0 amicroRNAs exhibit high frequency genomic alterations in human ca c2006 Jun 13 a9136-410 v1033 aMicroRNAs (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.
10aBreast Neoplasms10aFemale10aGene Dosage10aGene Expression Profiling10aHumans10aMicroRNAs10aNeoplasms10aNucleic Acid Hybridization10aOligonucleotide Array Sequence Analysis10aOvarian Neoplasms10aStatistics as Topic1 aZhang, Lin1 aHuang, Jia1 aYang, Nuo1 aGreshock, Joel1 aMegraw, Molly, S1 aGiannakakis, Antonis1 aLiang, Shun1 aNaylor, Tara, L1 aBarchetti, Andrea1 aWard, Michelle, R1 aYao, George1 aMedina, Angelica1 aO'brien-Jenkins, Ann1 aKatsaros, Dionyssios1 aHatzigeorgiou, Artemis1 aGimotty, Phyllis, A1 aWeber, Barbara, L1 aCoukos, George uhttp://megraw.cgrb.oregonstate.edu/node/332