Artículo

Pasquali, L.; Gaulton, K.J.; Rodríguez-Seguí, S.A.; Mularoni, L.; Miguel-Escalada, I.; Akerman, I.; Tena, J.J.; Morán, I.; Gómez-Marín, C.; Van De Bunt, M.; Ponsa-Cobas, J.; Castro, N.; Nammo, T.; Cebola, I.; García-Hurtado, J.; Maestro, M.A.; Pattou, F.; Piemonti, L. (...) Ferrer, J. "Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants" (2014) Nature Genetics. 46(2):136-143
Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Type 2 diabetes affects over 300 million people, causing severe complications and premature death, yet the underlying molecular mechanisms are largely unknown. Pancreatic islet dysfunction is central in type 2 diabetes pathogenesis, and understanding islet genome regulation could therefore provide valuable mechanistic insights. We have now mapped and examined the function of human islet cis-regulatory networks. We identify genomic sequences that are targeted by islet transcription factors to drive islet-specific gene activity and show that most such sequences reside in clusters of enhancers that form physical three-dimensional chromatin domains. We find that sequence variants associated with type 2 diabetes and fasting glycemia are enriched in these clustered islet enhancers and identify trait-associated variants that disrupt DNA binding and islet enhancer activity. Our studies illustrate how islet transcription factors interact functionally with the epigenome and provide systematic evidence that the dysregulation of islet enhancers is relevant to the mechanisms underlying type 2 diabetes. © 2014 Nature America, Inc.

Registro:

Documento: Artículo
Título:Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants
Autor:Pasquali, L.; Gaulton, K.J.; Rodríguez-Seguí, S.A.; Mularoni, L.; Miguel-Escalada, I.; Akerman, I.; Tena, J.J.; Morán, I.; Gómez-Marín, C.; Van De Bunt, M.; Ponsa-Cobas, J.; Castro, N.; Nammo, T.; Cebola, I.; García-Hurtado, J.; Maestro, M.A.; Pattou, F.; Piemonti, L.; Berney, T.; Gloyn, A.L.; Ravassard, P.; Skarmeta, J.L.G.; Müller, F.; Mccarthy, M.I.; Ferrer, J.
Filiación:Genomic Programming of Beta-Cells Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
CIBERDEM, Barcelona, Spain
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
Oxford Centre for Diabetes,Endocrinology and Metabolism, Churchill Hospital, Oxford, United Kingdom
Oxford National Institute for Health Research (NIHR) Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom
School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas, Universidad Pablo de Olavide-Junta de Andalucía, Seville, Spain
Department of Medicine, Imperial College London, London, United Kingdom
University of Lille 2, INSERM U859 Biotherapies of Diabetes, Lille, France
Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy
Department of Surgery, Geneva University Hospitals, University of Geneva, Geneva, Switzerland
Centre de Recherche de l'Institut du Cerveau et de la Moelle, Biotechnology and Biotherapy Team, University Pierre et Marie Curie, Paris, France
Instituto de Fisiología, Biología Molecular y Neurociencias IFIBYNE, Universidad de Buenos Aires, Buenos Aires, Argentina
Department of Metabolic Disorder, National Center for Global Health and Medicine, Research Institute, Shinjuku-ku, Tokyo, Japan
Palabras clave:glucose; transcription factor; article; chromatin; controlled study; DNA binding; enhancer region; epigenetics; gene cluster; gene control; gene disruption; gene sequence; genetic association; genetic risk; genetic variability; glucose blood level; human; non insulin dependent diabetes mellitus; nonhuman; pancreas insufficiency; pancreas islet; pathogenesis; priority journal; Base Sequence; Chromatin; Chromatin Immunoprecipitation; Diabetes Mellitus, Type 2; Electrophoretic Mobility Shift Assay; Enhancer Elements, Genetic; Formaldehyde; Gene Expression Regulation; Gene Regulatory Networks; Genome-Wide Association Study; Humans; Islets of Langerhans; Molecular Sequence Data; Sequence Analysis, RNA; Transcription Factors; Web Browser
Año:2014
Volumen:46
Número:2
Página de inicio:136
Página de fin:143
DOI: http://dx.doi.org/10.1038/ng.2870
Título revista:Nature Genetics
Título revista abreviado:Nat. Genet.
ISSN:10614036
CODEN:NGENE
CAS:glucose, 50-99-7, 84778-64-3
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10614036_v46_n2_p136_Pasquali

Referencias:

  • Rada-Iglesias, A., A unique chromatin signature uncovers early developmental enhancers in humans (2011) Nature, 470, pp. 279-283
  • Heintzman, N.D., Histone modifications at human enhancers reflect global cell-Type-specific gene expression (2009) Nature, 459, pp. 108-112
  • Creyghton, M.P., Histone H3K27ac separates active from poised enhancers and predicts developmental state (2010) Proc. Natl. Acad. Sci. USA, 107, pp. 21931-21936
  • Bonn, S., Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development (2012) Nat. Genet, 44, pp. 148-156
  • Gaulton, K.J., A map of open chromatin in human pancreatic islets (2010) Nat. Genet, 42, pp. 255-259
  • Shen, Y., A map of the cis-regulatory sequences in the mouse genome (2012) Nature, 488, pp. 116-120
  • An integrated encyclopedia of DNA elements in the human genome (2012) Nature, 489, pp. 57-74. , ENCODE Project Consortium
  • Kahn, S.E., Clinical review 135: The importance of β-cell failure in the development and progression of type 2 diabetes (2001) J. Clin. Endocrinol. Metab, 86, pp. 4047-4058
  • Lyssenko, V., Clinical risk factors, DNA variants, and the development of type 2 diabetes (2008) N. Engl. J. Med, 359, pp. 2220-2232
  • Ashcroft, F.M., Rorsman, P., Diabetes mellitus and the β cell: The last ten years (2012) Cell, 148, pp. 1160-1171
  • Bhandare, R., Genome-wide analysis of histone modifications in human pancreatic islets (2010) Genome Res, 20, pp. 428-433
  • Stitzel, M.L., Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci (2010) Cell Metab, 12, pp. 443-455
  • Khoo, C., Research resource: The Pdx1 cistrome of pancreatic islets (2012) Mol. Endocrinol, 26, pp. 521-533
  • Bernstein, B.E., The nih roadmap epigenomics mapping consortium (2010) Nat. Biotechnol, 28, pp. 1045-1048
  • Zhu, J., Genome-wide chromatin state transitions associated with developmental and environmental cues (2013) Cell, 152, pp. 642-654
  • Tennant, B.R., Identification and analysis of murine pancreatic islet enhancers (2013) Diabetologia, 56, pp. 542-552
  • Artner, I., MafB is required for islet β cell maturation (2007) Proc. Natl. Acad. Sci. USA, 104, pp. 3853-3858
  • Ahlgren, U., Jonsson, J., Jonsson, L., Simu, K., Edlund, H., β-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the β-cell phenotype and maturity onset diabetes (1998) Genes Dev, 12, pp. 1763-1768
  • Sander, M., Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of β-cell formation in the pancreas (2000) Development, 127, pp. 5533-5540
  • Sund, N.J., Tissue-specific deletion of Foxa2 in pancreatic β cells results in hyperinsulinemic hypoglycemia (2001) Genes Dev, 15, pp. 1706-1715
  • Sussel, L., Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic β cells (1998) Development, 125, pp. 2213-2221
  • Servitja, J.M., Ferrer, J., Transcriptional networks controlling pancreatic development and β cell function (2004) Diabetologia, 47, pp. 597-613
  • Wilson, M.E., Scheel, D., German, M.S., Gene expression cascades in pancreatic development (2003) Mech. Dev, 120, pp. 65-80
  • Oliver-Krasinski, J.M., Stoffers, D.A., On the origin of the β cell (2008) Genes Dev, 22, pp. 1998-2021
  • Gerstein, M.B., Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project (2010) Science, 330, pp. 1775-1787
  • Kyrmizi, I., Plasticity and expanding complexity of the hepatic transcription factor network during liver development (2006) Genes Dev, 20, pp. 2293-2305
  • Jin, C., H3.3/H2A.Z double variant-containing nucleosomes mark 'nucleosome-free regions' of active promoters and other regulatory regions (2009) Nat. Genet, 41, pp. 941-945
  • Ong, C.T., Corces, V.G., Enhancer function: New insights into the regulation of tissue-specific gene expression (2011) Nat. Rev. Genet, 12, pp. 283-293
  • Morán, I., Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes (2012) Cell Metab, 16, pp. 435-448
  • Stefflova, K., Cooperativity and rapid evolution of cobound transcription factors in closely related mammals (2013) Cell, 154, pp. 530-540
  • Zinzen, R.P., Girardot, C., Gagneur, J., Braun, M., Furlong, E.E., Combinatorial binding predicts spatio-Temporal cis-regulatory activity (2009) Nature, 462, pp. 65-70
  • Zhou, Q., Brown, J., Kanarek, A., Rajagopal, J., Melton, D.A., In vivo reprogramming of adult pancreatic exocrine cells to β-cells (2008) Nature, 455, pp. 627-632
  • Noordermeer, D., The dynamic architecture of Hox gene clusters (2011) Science, 334, pp. 222-225
  • Ernst, J., Mapping and analysis of chromatin state dynamics in nine human cell types (2011) Nature, 473, pp. 43-49
  • Smith, S.B., Rfx6 directs islet formation and insulin production in mice and humans (2010) Nature, 463, pp. 775-780
  • Zaret, K.S., Pioneer factors, genetic competence, and inductive signaling: Programming liver and pancreas progenitors from the endoderm (2008) Cold Spring Harb. Symp. Quant. Biol, 73, pp. 119-126
  • Scott, R.A., Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways (2012) Nat. Genet, 44, pp. 991-1005
  • Morris, A.P., Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes (2012) Nat. Genet, 44, pp. 981-990
  • Hindorff, L.A., A Catalog of Published Genome-Wide Association Studies, , http://www.genome.gov/26525384
  • El-Assaad, W., Saturated fatty acids synergize with elevated glucose to cause pancreatic β-cell death (2003) Endocrinology, 144, pp. 4154-4163
  • Shimabukuro, M., Zhou, Y.T., Levi, M., Unger, R.H., Fatty acid-induced β cell apoptosis: A link between obesity and diabetes (1998) Proc. Natl. Acad. Sci. USA, 95, pp. 2498-2502
  • Hu, L., Regulation of lipolytic activity by long-chain acyl-coenzyme A in islets and adipocytes (2005) Am. J. Physiol. Endocrinol. Metab, 289, pp. E1085-E1092
  • Helgason, A., Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution (2007) Nat. Genet, 39, pp. 218-225
  • Cho, Y.S., Meta-Analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians (2012) Nat. Genet, 44, pp. 67-72
  • Zaret, K.S., Grompe, M., Generation and regeneration of cells of the liver and pancreas (2008) Science, 322, pp. 1490-1494
  • Whyte, W.A., Master transcription factors and mediator establish super-enhancers at key cell identity genes (2013) Cell, 153, pp. 307-319
  • Lovén, J., Selective inhibition of tumor oncogenes by disruption of super-enhancers (2013) Cell, 153, pp. 320-334
  • Maurano, M.T., Systematic localization of common disease-Associated variation in regulatory DNA (2012) Science, 337, pp. 1190-1195
  • Trynka, G., Chromatin marks identify critical cell types for fine mapping complex trait variants (2013) Nat. Genet, 45, pp. 124-130
  • Heinz, S., Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities (2010) Mol. Cell, 38, pp. 576-589
  • Seo, S., Lim, J.W., Yellajoshyula, D., Chang, L.W., Kroll, K.L., Neurogenin and NeuroD direct transcriptional targets and their regulatory enhancers (2007) EMBO J., 26, pp. 5093-5108
  • Bucher, P., Assessment of a novel two-component enzyme preparation for human islet isolation and transplantation (2005) Transplantation, 79, pp. 91-97
  • McCulloch, L.J., GLUT2 (SLC2A2) is not the principal glucose transporter in human pancreatic β cells: Implications for understanding genetic association signals at this locus (2011) Mol. Genet. Metab, 104, pp. 648-653
  • Servitja, J.M., Hnf1a (MODY3) controls tissue-specific transcriptional programs and exerts opposed effects on cell growth in pancreatic islets and liver (2009) Mol. Cell. Biol, 29, pp. 2945-2959
  • Van Arensbergen, J., Derepression of Polycomb targets during pancreatic organogenesis allows insulin-producing β-cells to adopt a neural gene activity program (2010) Genome Res, 20, pp. 722-732
  • Langmead, B., Trapnell, C., Pop, M., Salzberg, S.L., Ultrafast and memory-efficient alignment of short DNA sequences to the human genome (2009) Genome Biol, 10, pp. R25
  • Zhang, Y., Model-based analysis of ChIP-Seq (MACS (2008) Genome Biol, 9, pp. R137
  • De Hoon, M.J., Imoto, S., Nolan, J., Miyano, S., Open source clustering software (2004) Bioinformatics, 20, pp. 1453-1454
  • McLean, C.Y., GREAT improves functional interpretation of cis-regulatory regions (2010) Nat. Biotechnol, 28, pp. 495-501
  • Blechinger, S.R., The heat-inducible zebrafish hsp70 gene is expressed during normal lens development under non-stress conditions (2002) Mech. Dev, 112, pp. 213-215
  • Meng, A., Tang, H., Ong, B.A., Farrell, M.J., Lin, S., Promoter analysis in living zebrafish embryos identifies a cis-Acting motif required for neuronal expression of GATA-2 (1997) Proc. Natl. Acad. Sci. USA, 94, pp. 6267-6272
  • Ravassard, P., A genetically engineered human pancreatic β cell line exhibiting glucose-inducible insulin secretion (2011) J. Clin. Invest, 121, pp. 3589-3597
  • Subramanian, A., Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles (2005) Proc. Natl. Acad. Sci. USA, 102, pp. 15545-15550
  • Tena, J.J., An evolutionarily conserved three-dimensional structure in the vertebrate Irx clusters facilitates enhancer sharing and coregulation (2011) Nat. Commun, 2 (310)
  • Splinter, E., De Wit, E., Van De Werken, H.J., Klous, P., De Laat, W., Determining long-range chromatin interactions for selected genomic sites using 4C-seq technology: From fixation to computation (2012) Methods, 58, pp. 221-230
  • Rozen, S., Skaletsky, H., Primer3 on the WWW for general users and for biologist programmers (2000) Methods Mol. Biol, 132, pp. 365-386
  • Boj, S.F., Parrizas, M., Maestro, M.A., Ferrer, J., A transcription factor regulatory circuit in differentiated pancreatic cells (2001) Proc. Natl. Acad. Sci. USA, 98, pp. 14481-14486
  • Gupta, S., Stamatoyannopoulos, J.A., Bailey, T.L., Noble, W.S., Quantifying similarity between motifs (2007) Genome Biol, 8, pp. R24
  • Rosenbloom, K.R., ENCODE data in the UCSC Genome Browser: Year 5 update (2013) Nucleic Acids Res, 41, pp. D56-D63
  • A user's guide to the encyclopedia of DNA elements (ENCODE (2011) PLoS Biol, 9, pp. e1001046. , ENCODE Project Consortium
  • Hansen, K.D., Irizarry, R.A., Wu, Z., Removing technical variability in RNA-seq data using conditional quantile normalization (2012) Biostatistics, 13, pp. 204-216

Citas:

---------- APA ----------
Pasquali, L., Gaulton, K.J., Rodríguez-Seguí, S.A., Mularoni, L., Miguel-Escalada, I., Akerman, I., Tena, J.J.,..., Ferrer, J. (2014) . Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants. Nature Genetics, 46(2), 136-143.
http://dx.doi.org/10.1038/ng.2870
---------- CHICAGO ----------
Pasquali, L., Gaulton, K.J., Rodríguez-Seguí, S.A., Mularoni, L., Miguel-Escalada, I., Akerman, I., et al. "Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants" . Nature Genetics 46, no. 2 (2014) : 136-143.
http://dx.doi.org/10.1038/ng.2870
---------- MLA ----------
Pasquali, L., Gaulton, K.J., Rodríguez-Seguí, S.A., Mularoni, L., Miguel-Escalada, I., Akerman, I., et al. "Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants" . Nature Genetics, vol. 46, no. 2, 2014, pp. 136-143.
http://dx.doi.org/10.1038/ng.2870
---------- VANCOUVER ----------
Pasquali, L., Gaulton, K.J., Rodríguez-Seguí, S.A., Mularoni, L., Miguel-Escalada, I., Akerman, I., et al. Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants. Nat. Genet. 2014;46(2):136-143.
http://dx.doi.org/10.1038/ng.2870