Programa De Postgrado En Biomedicina Y Biotecnología

Total Page:16

File Type:pdf, Size:1020Kb

Programa De Postgrado En Biomedicina Y Biotecnología E PROGRAMA DE POSTGRADO EN BIOMEDICINA Y BIOTECNOLOGÍA TRANSCRIPTOMIC ANALYSIS OF HOST-PATHOGEN RELATIONSHIP IN Vibrio vulnificus Memoria presentada por Carla Hernández Cabañero para optar al grado de Doctor con mención internacional por la Universidad de Valencia Dirigida por Dra. Carmen Amaro González Valencia, 2019 La Dra. Carmen Amaro González, catedrática del departamento de Microbiología y Ecología y directora del grupo de Patógenos Acuáticos del Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BIOTECMED), ambos de la Universidad de Valencia, certifica que Dña. Carla Hernández Cabañero ha realizado bajo su dirección el trabajo titulado “Transcriptomic analysis of host-pathogen relathionship in Vibrio vulnificus” y autoriza la lectura y defensa de la misma para optar al grado de Doctor en Ciencias Biológicas por la Universidad de Valencia. Y para que así conste a los efectos oportunos, firma la presente en Valencia en Octubre de 2019. Fdo. Carmen Amaro González La Dra. Belén Fouz Rodríguez, profesora contratada del departamento de Microbiología y Ecología y miembro del grupo de Patógenos Acuáticos del Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BIOTECMED), ambos de la Universidad de Valencia, certifica que Dña. Carla Hernández Cabañero ha realizado bajo su tutela el trabajo titulado “Transcriptomic analysis of host-pathogen relathionship in Vibrio vulnificus” y autoriza la lectura y defensa de la misma para optar al grado de Doctor en Ciencias Biológicas por la Universidad de Valencia. Y para que así conste a los efectos oportunos, firma la presente en Valencia en Octubre de 2019. Fdo. Belén Fouz Rodríguez “La imaginación es, por excelencia, la habilidad de descubrir, es aquello que penetra en los mundos invisibles que nos rodean, los mundos de la ciencia.” Ada Lovelace “Como investigadora, los momentos inolvidables de mi vida son excepcionales… Cuando el velo que esconde los secretos de la naturaleza de repente se levanta.” Gerty Cory “Por encima de todo, no temas los momentos difíciles. De ellos sale lo mejor.” Rita Levi-Montalcini AGRADECIMIENTOS/ ACKNOWLEDGEMENTS Me gustaría aprovechar este espacio para dedicar unas líneas a todas las personas que en mayor o menor medida han contribuido a esta tesis, porque si algo tengo claro es que de no haber sido por todos vosotros la finalización de este proyecto no habría sido posible. Por ello, espero consideréis este trabajo tan vuestro como mío. Mi más sincero agradecimiento a mi directora, Carmen Amaro, no solo por haberme dado la oportunidad de formarme en el laboratorio durante el máster y posteriormente haber confiado en mí para la realización de este tesis, sino también por la confianza y el buen trato personal que me has dado durante todos estos años. A Belén Fouz. Supongo que de no haber realizado el TFG contigo no habría terminado trabajando en este laboratorio, así que en primer lugar gracias por eso. Gracias también por ser la tutora de esta tesis, y por los consejos que me has dado durante estos años, tanto en lo referente al trabajo con peces como en las tareas docentes. Tengo que admitir que las prácticas del máster de acuicultura han sido mis favoritas. A todos los compañeros del laboratorio. A los que estaban en un principio, por acogerme como a una más desde el primer momento: a David por ser mi guía en los inicios (sin duda alguna tú me enseñaste a trabajar en el laboratorio); a Miguel por las tardes de temazos y los refranes en Valencià; a Celia, por enseñarme a contar células, calcular mois y hacer qPCRs, y por seguir interesándote por mis avances cuando ya habías dejado el lab; a Amparo, por estar siempre ahí para escuchar, charrar y echar una mano, gracias también por enseñarme a trabajar con animales, desde sangrar conejos hasta muestrear anguilas; y a Eva, por tener siempre respuesta a todas, todas mis dudas. También a los compañeros que han ido llegando después, en especial a Paco, desde el máster sufriendo (y ahogando las penas en cerveza) juntos; y a Vero, mi primera estudiante y una gran ayuda durante dos años (todavía te echo de menos). También a Duarte (por el mes de agosto que pasamos juntos trabajando con Chung- Te), Eli, Amparo Jr., Ana, Omar, Carla Jr., Adrián, Sara, Héctor… En definitiva, a todos los que habéis pasado por el lab, porque todos habéis dejado vuestra huella y me habéis ayudado en algún momento. También a Alba, aunque no de lab sí compañera de despacho. A los compañeros de departamento que me han ayudado, especialmente a Eduardo (por el hielo seco y las medidas de oxígeno) y a Chelo, por ayudarme en los primeros años de docencia. 9 A Rodolfo, por proporcionarme las anguilas y a Lucas y Silvia por su colaboración en las infecciones realizadas en planta de acuarios. También al servicio de secuenciación, en especial a Amparo, por resolver las dudas que me han surgido a lo largo de los años y por prestarme reactivos cuando ha sido necesario. Gracias al grupo de fisiología de peces de la UAB, especialmente a Lluis Tort por permitirme pasar tres meses en su grupo y por supuesto a Felipe y Eva, que no solo me enseñasteis a trabajar con las muestras y datos de microarray sino que me hicisteis sentir como una más cada día que pasé en el laboratorio/despacho. Gracias a los dos también por haber estado siempre dispuestos a un Skype cuando he necesitado reanalizar algunos datos. De la estancia en Barcelona gracias también a mi prima Julia, por tan generosamente acogerme en tu casa y regalarme tantas risas y buenos recuerdos que me llevo conmigo. My second stage was in Blokesch’s Lab in EPFL (Switzerland), so thank you very much Melanie for letting me stay with you and your wonderful group for three months and learn so many things. I really appreciate that you treated me as a member of your group inviting me to both lab and personal meetings. I would also like to thank all the lab mates I met there for the kindly personal trait they gave me not only in the lab, but also in the coffee breaks, lunch time, beer time, dinner time, cinema time… Thank you all for made me feel like anyone else in the group. I’m especially grateful to Audrey and Natàlia for finding me some space in the P2.2 and teaching me everything I know about amoeba and confocal microscopy; and Leonardo for practicing your Spanish with me and giving me a break of English speaking. Thank you also to the FSLE building mates, especially to Olivier, for sharing the earliest and darkest breakfasts I have had in my live, and to Giovanni for being the light in that depressing building and make my days during the last month in Lausanne (you are soooo Italian!). Probably we will NEVER EVER meet again but I wish you all the best guys. A mis amigas, Lucía, Bea, Miriam, Rocío y Ana. Porque aunque cada vez nos juntemos menos (por la tesis y otras circunstancias) seguimos estando ahí las unas para las otras. A mi grupo paranormaaaaal (¿de verdad vamos a dejar esto como nombre de grupo para la eternidad?). Cris, Vicent, Víctor (estoy absolutamente convencida de que nadie me ha preguntado tanto “¿CÓMO VA LA TESIS?” como tú) y Álvaro, porque aunque penséis que soy una asesina de anguilas, con vosotros siempre he podido desconectar de la tesis. A Víctor también le agradezco las clases de Python (quizá no te lo creas, pero me han ayudado a entender muchas cosas). 10 A los compañeros de carrera que acabaron siendo amigos, Cris (otra vez), Edgar, David y Elena (aunque nos veamos poquísimo). También a Juan y los compañeros de excursiones, que con el tiempo se han cambiado por horchatas y chocolates. A TODA mi familia (¡y somos muchos!), al Gen Hernández, a los Cabañero y a los postizos (los García-Navarro y Martínez-Cantos). Gracias a todos por formar parte de mi vida durante tantos años. Mención especial a mi tía Ana (una mezcla entre segunda madre y hermana mayor), gracias por fundar la casa del Joe y la beca Hernández, que me dieron cobijo en Valencia durante 6 años, por los viajes, las clases de estadística, de flamenco… gracias por todo. Y a Marta, por los años (y locuras) compartidos en la casa del Joe, y especialmente por ocuparse del diseño de la portada de esta tesis. También a los peludos de 4 patas de la familia que dan tanto sin pedir nada, los que están y los que ya no están, pero que nos han alegrado la vida compartiendo paseos y siestas con nosotros. A mis padres, por haber echo de mí la persona que soy, por enseñarme que la constancia y el esfuerzo son las mejores armas para luchar y conseguir mis objetivos, por animarme y apoyarme (sentimental y económicamente) en todas mis decisiones, y en los últimos años, por preocuparos de si se morían o no las anguilas y/o “los bichos”. Sin vosotros no habría llegado hasta aquí. Gracias también por haberme dado la mejor amiga que podría tener, mi hermana, porque pese a ser tan distintas (o no) no se me ocurre nadie mejor con quien compartir momentos (buenos y malos) en la vida, ya sea juntas en casa o en la distancia. A Álvaro, por cargar conmigo la peor parte de esta tesis, por aguantar mi interminable verborrea sobre microarrays, qPCRs, genes y mutantes (sobre todo los días en que llegaba a casa cabreada), aceptando también las estancias que nos han separado a temporadas, los domingos de laboratorio, los fines de semana de escritura de tesis… En definitiva, gracias por cruzarte en mi vida y quedarte en ella.
Recommended publications
  • High-Mobility Group A1 Proteins May Be Involved in Estrogen Receptor Status of Breast Cancer
    3786 Editorial Commentary High-mobility group A1 proteins may be involved in estrogen receptor status of breast cancer Yoshihiro Harada, Kenji Ohe Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Fukuoka University, Jonan-ku, Fukuoka, Japan Correspondence to: Kenji Ohe. Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Fukuoka University, Building 17, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-180, Japan. Email: [email protected]. Provenance and Peer Review: This article was commissioned by the editorial office, Translational Cancer Research. The article did not undergo external peer review. Comment on: Gorbounov M, Carleton NM, Asch-Kendrick RJ, et al. High mobility group A1 (HMGA1) protein and gene expression correlate with ER-negativity and poor outcomes in breast cancer. Breast Cancer Res Treat 2020;179:25-35. Submitted Apr 27, 2020. Accepted for publication May 13, 2020. doi: 10.21037/tcr-20-1921 View this article at: http://dx.doi.org/10.21037/tcr-20-1921 The three types of breast cancer HMGA1 proteins: old and new proteins in breast cancer Breast cancer is one of the most common of cancers in woman. About 316,700 new cases were diagnosed as breast HMGA1 (previously called HMGI/Y) is a member of the cancer in US woman in 2019 and 41,760 were predicted to high-mobility group (HMG) proteins that were found from die from it (1). Breast cancer has a characteristic of therapy- their high mobility characteristics during polyacrylamide targeting receptors: hormone receptors (HR) that are electrophoresis of non-histone chromatin-associated estrogen receptor [ER: human ERα protein (NCBI protein proteins (3).
    [Show full text]
  • An Ontogenetic Switch Drives the Positive and Negative Selection of B Cells
    An ontogenetic switch drives the positive and negative selection of B cells Xijin Xua, Mukta Deobagkar-Lelea, Katherine R. Bulla, Tanya L. Crockforda, Adam J. Meadb, Adam P. Cribbsc, David Simsc, Consuelo Anzilottia, and Richard J. Cornalla,1 aMedical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom; bMedical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom; and cMedical Research Council, Weatherall Institute of Molecular Medicine, Centre for Computational Biology, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom Edited by Michael Reth, University of Freiburg, Freiburg, Germany, and approved January 6, 2020 (received for review September 3, 2019) + Developing B cells can be positively or negatively selected by self- BM HSCs increased CD5 B-1a B cell development (15), while antigens, but the mechanisms that determine these outcomes are expression of let-7b in FL pro-B cells blocked the development of incompletely understood. Here, we show that a B cell intrinsic B-1 B cells (17). These findings support the notion of hard-wired switch between positive and negative selection during ontogeny differences during ontogeny, but possibly downstream of the HSC is determined by a change from Lin28b to let-7 gene expression. commitment stage. Ectopic expression of a Lin28b transgene in murine B cells restored Several lines of evidence also suggest that B-1 B cells can un- the positive selection of autoreactive B-1 B cells by self-antigen in dergo positive selection, which is linked to their B cell receptor adult bone marrow.
    [Show full text]
  • HMGA2 Promotes Adipogenesis by Activating C/EBP&Beta
    CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector Biochemical and Biophysical Research Communications 472 (2016) 617e623 Contents lists available at ScienceDirect Biochemical and Biophysical Research Communications journal homepage: www.elsevier.com/locate/ybbrc HMGA2 promotes adipogenesis by activating C/EBPb-mediated expression of PPARg * Yang Xi a, Wanjing Shen a, Lili Ma a, Ming Zhao a, Jiachen Zheng a, Shizhong Bu a, , ** Shinjiro Hino b, Mitsuyoshi Nakao b, c, a Diabetes Center, and Zhejiang Provincial Key Laboratory of Pathophysiology, Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo 315211, China b Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, 860-0811, Japan c Core Research for Evolutional Science and Technology (CREST), Japan Agency for Medical Research and Development, Tokyo, Japan article info abstract Article history: Adipogenesis is orchestrated by a highly ordered network of transcription factors including peroxisome- Received 1 March 2016 proliferator activated receptor-gamma (PPARg) and CCAAT-enhancer binding protein (C/EBP) family Accepted 6 March 2016 proteins. High mobility group protein AT-hook 2 (HMGA2), an architectural transcription factor, has been Available online 8 March 2016 reported to play an essential role in preadipocyte proliferation, and its overexpression has been impli- cated in obesity in mice and humans. However, the direct role of HMGA2 in regulating the gene Keywords: expression program during adipogenesis is not known. Here, we demonstrate that HMGA2 is required for Adipogenesis C/EBPb-mediated expression of PPARg, and thus promotes adipogenic differentiation. We observed a HMGA2 C/EBPb transient but marked increase of Hmga2 transcript at an early phase of differentiation of mouse 3T3-L1 PPARg preadipocytes.
    [Show full text]
  • The Expression of HMGA Genes Is Regulated by Their 3Оutr
    Oncogene (2001) 20, 4537 ± 4541 ã 2001 Nature Publishing Group All rights reserved 0950 ± 9232/01 $15.00 www.nature.com/onc The expression of HMGA genes is regulated by their 3'UTR Lars Borrmann1, S Wilkening1 and J Bullerdiek*,1 1Center for Human Genetics, University of Bremen, Leobenerstr. ZHG, 28359 Bremen, Germany Many benign mesenchymal tumors are characterized by binding by HMGA proteins leads to a conformational chromosomal abnormalities of the regions 12q15 or change in DNA modulating the environment for the 6p21.3 leading to aberrant expression of either HMGA2 binding of transcription factors. (formerly HMGIC) or HMGA1 (formerly HMGIY). Whereas HMGA2 is almost exclusively expressed in The proteins of both genes belong to the HMGA proliferating undierentiated cells during embryogen- (formerly HMGI(Y)) family of architectural transcrip- esis and in benign and malignant tumors, HMGA1 can tion factors. As a rule, aberrant HMGA transcripts also be detected at very low levels in dierentiated cells found in a variety of benign tumors have intact coding (Chiappetta et al., 1996; Zhou et al., 1995; Busse- regions at least for the DNA binding domains with a makers et al., 1991; Abe et al., 2000). An increased truncation of their 3' untranslated regions. Adding this to HMGA1 gene expression has been considered as a the ®nding that an altered HMGA protein level is not general diagnostic marker for neoplastic transforma- always correlated with an increased amount of corre- tion (Goodwin et al., 1985; Giancotti et al., 1987, 1989) sponding mRNA indicates a posttranscriptional expres- and the metastatic potential of malignant neoplasms sion control mediated by regulatory elements within the (Bussemakers et al., 1991; Tamimi et al., 1993; 3'UTR.
    [Show full text]
  • Supplementary Table 1
    Supplementary Table 1 gene p_val avg_logFC pct.1 pct.2 p_val_adj cluster gene gene p_val avg_logFC pct.1 pct.
    [Show full text]
  • Dynamics of H3k27me3 Modification on Plant Adaptation To
    plants Review Dynamics of H3K27me3 Modification on Plant Adaptation to Environmental Cues Qingwen Shen , Yisheng Lin, Yingbo Li and Guifeng Wang * National Key Laboratory of Wheat and Maize Crops Science, CIMMYT-China (Henan) Joint Research Center of Wheat and Maize, Collaborative Innovation Center of Henan Grain Crops, College of Agronomy, Henan Agricultural University, Zhengzhou 450002, China; [email protected] (Q.S.); [email protected] (Y.L.); [email protected] (Y.L.) * Correspondence: [email protected]; Tel.: +86-371-56990324 Abstract: Given their sessile nature, plants have evolved sophisticated regulatory networks to confer developmental plasticity for adaptation to fluctuating environments. Epigenetic codes, like tri- methylation of histone H3 on Lys27 (H3K27me3), are evidenced to account for this evolutionary benefit. Polycomb repressive complex 2 (PRC2) and PRC1 implement and maintain the H3K27me3- mediated gene repression in most eukaryotic cells. Plants take advantage of this epigenetic machinery to reprogram gene expression in development and environmental adaption. Recent studies have uncovered a number of new players involved in the establishment, erasure, and regulation of H3K27me3 mark in plants, particularly highlighting new roles in plants’ responses to environmental cues. Here, we review current knowledge on PRC2-H3K27me3 dynamics occurring during plant growth and development, including its writers, erasers, and readers, as well as targeting mechanisms, and summarize the emerging roles of H3K27me3 mark in plant adaptation to environmental stresses. Citation: Shen, Q.; Lin, Y.; Li, Y.; Wang, G. Dynamics of H3K27me3 Keywords: H3K27me3; epigenetics; environmental cues; polycomb repressive complex 2; polycomb Modification on Plant Adaptation to repressive complex 1; demethylase; recruitment Environmental Cues.
    [Show full text]
  • Hypoxia Inducible Factors in the Tumor Microenvironment As Therapeutic Targets of Cancer Stem Cells T
    Life Sciences 237 (2019) 116952 Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie Review article Hypoxia inducible factors in the tumor microenvironment as therapeutic targets of cancer stem cells T Farnaz Hajizadeha,b, Isobel Okoyec, Maryam Esmailyd, Mitra Ghasemi Chaleshtaria, Ali Masjedia, ∗ Gholamreza Azizie, Mahzad Irandousta, Ghasem Ghalamfarsaf, Farhad Jadidi-Niaraghg,h, a Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran b Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran c Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, T6G 2E1, Canada d Department of Medical Entomology and Vector Control, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran e Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran f Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran g Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran h Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran ARTICLE INFO ABSTRACT Keywords: Cancer stem cells (CSC) constitute a small area of the tumor mass and are characterized by self-renewal, dif- Cancer ferentiation and the ability to promote the development of secondary chemo-resistant tumors. Self-renewal of Hypoxia CSCs is regulated through various signaling pathways including Hedgehog, Notch, and Wnt/β-catenin pathways. Hypoxia inducible factor A few surface markers have been identified, which provide a means of targeting CSCs according to tumor type. Cancer stem cell Depending on the proximity of CSCs to the tumor hypoxic niche, hypoxia-inducible factors (HIFs) can play a critical role in modulating several CSC-related characteristics.
    [Show full text]
  • PIT1 Upregulation by HMGA Proteins Has a Role in Pituitary Tumorigenesis
    Endocrine-Related Cancer (2012) 19 123–135 PIT1 upregulation by HMGA proteins has a role in pituitary tumorigenesis Dario Palmieri1,2, Teresa Valentino1,2, Ivana De Martino1, Francesco Esposito1,2, Paolo Cappabianca3, Anne Wierinckx4,5, Michela Vitiello1,2, Gaetano Lombardi6, Annamaria Colao6, Jacqueline Trouillas4,5, Giovanna Maria Pierantoni1, Alfredo Fusco1,2 and Monica Fedele1,2 1Dipartimento di Biologia e Patologia Cellulare e Molecolare, 2Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS) del Consiglio Nazionale delle Ricerche and 3Dipartimento di Scienze Neurologiche, Divisione di Neurochirurgia, Universita` degli Studi di Napoli ‘Federico II’, via Pansini 5, 80131 Naples, Italy 4INSERM U1028; CNRS UMR5292; Lyon Neuroscience Research Center, Neuro-oncology and Neuro-inflammation Team, Lyon F-69372, France 5University Lyon1, F-69000 Lyon, France 6Dipartimento di Endocrinologia, Universita` degli Studi di Napoli ‘Federico II’, 80131 Naples, Italy (Correspondence should be addressed to A Fusco; Email: [email protected]) Abstract We have previously demonstrated that HMGA1B and HMGA2 overexpression in mice induces the development of GH and prolactin (PRL) pituitary adenomas mainly by increasing E2F1 transcriptional activity. Interestingly, these adenomas showed very high expression levels of PIT1, a transcriptional factor that regulates the gene expression of Gh, Prl, Ghrhr and Pit1 itself, playing a key role in pituitary gland development and physiology. Therefore, the aim of our study was to identify the role of Pit1 overexpression in pituitary tumour development induced by HMGA1B and HMGA2. First, we demonstrated that HMGA1B and HMGA2 directly interact with both PIT1 and its gene promoter in vivo, and that these proteins positively regulate Pit1 promoter activity, also co-operating with PIT1 itself.
    [Show full text]
  • Candidate Biomarkers of Resistance to Retinoids in Cell Lines Derived from Neuroblastoma
    FACULTY OF SCIENCE Candidate biomarkers of resistance to retinoids in cell lines derived from neuroblastoma Ph.D. Dissertation VIERA DOBROTKOVÁ Supervisor: RNDr. Petr Chlapek, DiS., Ph.D. Department of Experimental Biology Brno 2019 Bibliographic Entry Author: Mgr. Viera Dobrotková Faculty of Science, Masaryk University Department of Experimental Biology Title of Thesis: Candidate biomarkers of resistance to retinoids in cell lines derived from neuroblastoma Degree Programme: Biology Field of Study: Molecular and Cellular Biology Supervisor: RNDr. Petr Chlapek, DiS., Ph.D. Academic Year: 2018/2019 Number of Pages: 115+0 Keywords: Neuroblastoma; Retinoids; Candidate biomarkers; Resistance; Sensitivity; Differentiation therapy Bibliografický záznam Autorka: Mgr. Viera Dobrotková Přírodovědecká fakulta, Masarykova univerzita Ústav experimentální biologie Název práce: Kandidátní biomarkery rezistence k retinoidům u buněčných linií derivovaných z neuroblastomu Studijní program: Biologie Studijní obor: Molekulární a buněčná biologie Vedoucí práce: RNDr. Petr Chlapek, DiS., Ph.D. Akademický rok: 2018/2019 Počet stran: 115+0 Klíčová slova: Neuroblastom; Retinoidy; Kandidátní biomarkery; Rezistence; Senzitivita; Diferenciační terapie Abstract Retinoids are key compounds in differentiation therapy, mainly in acute promyelocytic leukemia and high-risk neuroblastoma. Despite their proven effectiveness in preventing tumor relapse and improving patient survival, resistance to this treatment represents the most limiting factor in achieving an adequate
    [Show full text]
  • WO 2015/048577 A2 April 2015 (02.04.2015) W P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/048577 A2 April 2015 (02.04.2015) W P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 48/00 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, PCT/US20 14/057905 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, 26 September 2014 (26.09.2014) KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (25) Filing Language: English PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (26) Publication Language: English SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/883,925 27 September 2013 (27.09.2013) US (84) Designated States (unless otherwise indicated, for every 61/898,043 31 October 2013 (3 1. 10.2013) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (71) Applicant: EDITAS MEDICINE, INC.
    [Show full text]
  • Global Analysis of Estrogen Receptor Beta Binding to Breast Cancer Cell Genome Reveals an Extensive Interplay with Estrogen Rece
    Grober et al. BMC Genomics 2011, 12:36 http://www.biomedcentral.com/1471-2164/12/36 RESEARCHARTICLE Open Access Global analysis of estrogen receptor beta binding to breast cancer cell genome reveals an extensive interplay with estrogen receptor alpha for target gene regulation Oli MV Grober1†, Margherita Mutarelli1†, Giorgio Giurato1, Maria Ravo1,2, Luigi Cicatiello1, Maria Rosaria De Filippo1, Lorenzo Ferraro1, Giovanni Nassa1,2, Maria Francesca Papa1, Ornella Paris1, Roberta Tarallo1,2, Shujun Luo3, Gary P Schroth3, Vladimir Benes4, Alessandro Weisz1,2* Abstract Background: Estrogen receptors alpha (ERa) and beta (ERb) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype of breast cancer (BC). The two receptors can be found co-expressed and play specific, often opposite, roles, with ERb being able to modulate the effects of ERa on gene transcription and cell proliferation. ERb is frequently lost in BC, where its presence generally correlates with a better prognosis of the disease. The identification of the genomic targets of ERb in hormone-responsive BC cells is thus a critical step to elucidate the roles of this receptor in estrogen signaling and tumor cell biology. Results: Expression of full-length ERb in hormone-responsive, ERa-positive MCF-7 cells resulted in a marked reduction in cell proliferation in response to estrogen and marked effects on the cell transcriptome. By ChIP-Seq we identified 9702 ERb and 6024 ERa binding sites in estrogen-stimulated cells, comprising sites occupied by either ERb,ERa or both ER subtypes. A search for TF binding matrices revealed that the majority of the binding sites identified comprise one or more Estrogen Response Element and the remaining show binding matrixes for other TFs known to mediate ER interaction with chromatin by tethering, including AP2, E2F and SP1.
    [Show full text]
  • The HMGA Proteins: a Myriad of Functions (Review)
    289-305 9/1/08 10:59 Page 289 INTERNATIONAL JOURNAL OF ONCOLOGY 32: 289-305, 2008 289 The HMGA proteins: A myriad of functions (Review) ISABELLE CLEYNEN and WIM J.M. VAN DE VEN Laboratory of Molecular Oncology, Department of Human Genetics, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium Received September 28, 2007; Accepted November 5, 2007 Abstract. The ‘high mobility group’ HMGA protein family 3. The HMGA genes and corresponding proteins consists of four members: HMGA1a, HMGA1b and HMGA1c, 4. The HMGA proteins: mechanism of action which result from translation of alternative spliced forms of 5 Cellular functions of the HMGA proteins one gene and HMGA2, which is encoded for by another 6. Regulation of HMGA expression gene. HMGA proteins are characterized by three DNA-binding 7. Conclusion domains, called AT-hooks, and an acidic carboxy-terminal tail. HMGA proteins are architectural transcription factors that both positively and negatively regulate the transcription 1. Introduction of a variety of genes. They do not display direct transcriptional activation capacity, but regulate gene expression by changing Life depends on the ability of a cell to store, retrieve, process the DNA conformation by binding to AT-rich regions in and translate the genetic instructions required to make and the DNA and/or direct interaction with several transcription maintain a living organism. This hereditary information is factors. In this way, they influence a diverse array of normal passed on from a cell to its daughter cells at cell division, and biological processes including cell growth, proliferation, from generation to generation of organisms through the differentiation and death.
    [Show full text]