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Session 6: Epigenetics Poster 3 Polyarginine peptide nucleic acids inibit biological activity of microRNA 210 Enrica Fabbri 1 , Nicoletta Bianchi 1 , Eleonora Brognara 1 ,Alessia Finotti 1 , Giulia Breveglieri 1 , Monica Borgatti 1 , Alex Manicardi 2 , Roberto Corradini 2 , Rosangela Marchelli 2 and Roberto Gambari 1 1 BioPharmaNet, Department of Biochemistry and Molecular Biology, Ferrara University, via Fossato di Mortara, 74, 44121, Ferrara, Italy, e-mail:gam@unife.it; 2 Department of Organic Chemistry, Parma University, Parco Area delle Scienze, 17/A, 43124 Parma, Italy. Peptide nucleic acids are DNA mimics extensively used for pharmacological regulation of gene expression in antisense and anti-gene therapies. At present, very few data are available on the use of PNAs as molecules targeting microRNAs. MicroRNAs are a family of small (19 to 25 nucleotide in length) noncoding RNAs that regulate gene expression by sequenceselective targeting of mRNAs, leading to a translational repression or mRNA degradation, depending on the degree of complementarity between microRNAs and the target sequences. MicroRNAs are deeply involved in the control of highly regulated biological functions, such as differentiation, cell cycle and apoptosis. The aim of the present study was to determine the activity of a PNA conjugated to polyarginine peptide and designed against microRNA 210, a microRNA associated to hypoxia and involved in the erythroid differentiation modulation. Our studies demonstrated that this PNA is efficiently internalized within target cells and strongly inhibits microRNA 210 activity with an alteration of the raptor and !-globin gene expression. Unlike commercially available antagomiRs, which need continous administrations, a single administration of this PNA (without using transfection reagents like lipofectin or lipofectamine) is sufficient to obtain these biological effects. Our results demostrate PNA-based molecules are very promising reagents to modulate the biological activity of micro RNAs. 128
Session 6: Epigenetics Poster 4 Dataset integration identifies transcriptional regulation of microRNA genes by PPARG in mouse adipogenesis Elisabeth John 1 , Anke Wienecke-Baldacchino 1 , Merja Heinäniemi 1 , Carsten Carlberg 1,2# and Lasse Sinkkonen 1 1 Life Sciences Research Unit, University of Luxembourg, L-1511 Luxembourg, Luxembourg 2 Department of Biosciences, University of Eastern Finland, FIN-70211 Kuopio, Finland E-mail: elisabeth.john@uni.lu, anke.wienecke@uni.lu, merja.heinäniemi@uni.lu, carsten.carlberg@uni.lu, lasse.sinkkonen@uni.lu Peroxisome proliferator-activated receptor G (PPARG) is a key transcription factor in mammalian adipogenesis. Genome-wide approaches identified thousands of PPARG binding sites in mature mouse 3T3-L1 adipocytes and PPARG up-regulates hundreds of proteincoding genes during adipogenesis. However, so far no microRNA (miRNA) genes were identified as primary PPARG targets. By integration of four separate datasets of genome-wide PPARG binding sites in 3T3-L1 adipocytes we identified 98 miRNA clusters with PPARG binding sites within 50 kb from miRNA gene transcription start sites. Nineteen of these putative PPARG-regulated mature miRNAs were up-regulated above 2-fold during 3T3-L1 adipogenesis. Focusing on miRNA loci with PPARG binding sites confirmed by at least three datasets resulted in six high confidence miRNA target loci. The up-regulation of five miRNA genes miR-103-1 (host gene Pank3), miR-148b (Copz1), miR-182/96/183, miR-205 and miR- 378 (Ppargc1b) followed that of Pparg. The PPARG dependence of four of these miRNA loci was demonstrated by PPARG knock-down. The loci of miR-103-1 (Pank3) and miR-378 (Ppargc1b) were also responsive to the PPARG ligand rosiglitazone. Finally, chromatin immunoprecipitation analysis validated three in silico predicted PPARG binding sites at the miR-103-1 locus and two at the miR-378 locus. In conclusion, we identified 22 putative PPARG target miRNAs genes, showed the PPARG dependence of four of these genes and demonstrated two as functional PPARG target genes in mouse adipogenesis. 129
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Luxembourg, January 26th to 28th, 2
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Luxembourg, January 26th to 28th, 2
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Preface In 1998, we organized the f
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European Research Institute for Int
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How to reach the congress center? -
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Many thanks to all exhibitors Pleas
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Wednesday January 26th, 2011 8h00 -
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Workshops 2 and Posters Session 2 1
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Oral presentations (In chronologica
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Activated Ras Requires Autophagy to
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DNA-damage stress response in femal
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Towards understanding of life and d
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Systems Analysis of Endocytosis by
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Whole genome scans in drosophila to
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Search for the effects of anticance
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Redox regulation of transcription f
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A dual role of JAK1: regulation of
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Immunity and death in chronic viral
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Study of the anti-apoptotic role of
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Proteomic phenotyping of the cell s
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Traveling to the Ends of the Proteo
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Site-Specific Identification of SUM
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Mechanisms of Epigenetics in Health
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MicroRNAs and erythroid differentia
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A Systems Approach to Modeling and
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Targeting the invasive phenotype us
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Genes related to energy metabolism
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Pathological aspects of vascular ag
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Control of class III PI3 kinase in
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p75NTR regulates A! deposition by i
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Workshop presentations 61
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Agilent Technologies New enrichment
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MAPTrix TM biomimetics from amsbio:
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2 1 Map and bus stops 3 4 Meeting C
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11 5 PARC DE L'EUROPE Dommeldange W
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A heart for cancer sick children To
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Wednesday January 26th Keynote sess
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Session 1: Cell death Poster 1 The
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Session 1: Cell death Poster 3 In v
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Session 1: Cell death Poster 5 Func
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Session 1: Cell death Poster 7 Mode
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Session 1: Cell death Poster 9 Prot
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Page 97 and 98: Session 1: Cell death Poster 13 Nit
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Page 103 and 104: Posters are classified by session a
Page 105 and 106: Session 2: Cell signaling Poster 2
Page 117 and 118: Session 3: Transcriptional control
Page 127 and 128: Session 4: Immunology Poster 2 Immu
Page 129 and 130: Session 4: Immunology Poster 4 Immu
Page 131 and 132: Session 4: Immunology Poster 6 Iden
Page 133 and 134: Session 4: Immunology Poster 8 Smal
Page 135 and 136: Session 4: Immunology Poster 10 INJ
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Page 139 and 140: Session 5: Proteomics Poster 1 Phos
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Page 149 and 150: Session 6: Epigenetics Poster 6 Fun
Page 151 and 152: Session 6: Epigenetics 8 Switching
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Page 157 and 158: Session 7: Cancer signaling network
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Page 195 and 196: Session 9: Neurodegenerative Diseas
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Session 9: Neurodegenerative diseas
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Notes 195
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List of participants (In alphabetic
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Mrs. Emilie Bana Laboratoire d'Ing
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Dr. Alessandro Corsaro Laboratory o
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Pr. Paul Fisher Microbial Cell Biol
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Mr. Kasper Hoebe Cincinnati Childre
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Mr. Hendrik Koopmans Cell Biology W
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Mr. Romuald Menth Technical Support
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Notes 218
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Notes 220
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We thank our sponsors:
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