A few words about epigenetics...

Welcome to the Epigenetics laboratory web page. Not so long ago the subject of epigenetics was considered an obscure discipline in cellular biology, an even more in cancer research. The "serious" researchers look at it with a certain concerned face. Today, those same researchers have enthusiastically embraced its study. A quick bibliographic search will show us the exponential increase in the articles published in the subject. Two discoveries were seminal in the current booming: the establishment that classical tumor suppressor genes undergo CpG island hypermethylation associated silencing in cancer cells and the characterization that chemical modification of histones were key steps in gene expression. From these two starting points the research picture has expanded to determine all the players in the epigenetics card game (DNA methyltransferases, Methyl-CpG binding proteins, histone deacetylases, histone methyltransferases, chromatin remodelling factors...), to study the consequences of epigenetic alterations for human biology (cloning, human genetic diseases such as Rett Syndrome and ICF...) and to search for epigenetic drugs against human pathologies, being the best examples the DNA demethylating agents and inhibitors of histone deacetylases. It is a young discipline, but with a terrific potential. I wish that our web page will be a useful tool to learns more about epigenetics, to share our research interests and to receive your comments and questions.My best wish,

Dr Manel Esteller
Director,
Epigenetics Laboratory,
Spanish National Cancer Center (CNIO)
E-mail: mesteller@cnio.es


Anouncements


Press Report

on Fraga et al. (PNAS 2005 July)
The Scientist 7-7-2005 "How epigenetics affects twins In genetically identical siblings, DNA methylation and histone acetylation correlate with age and lifestyle"
Fox News 6-7-2005 "Gene Activity May Vary in Identical Twins"
El Mundo 5-5-2005 "El envejecimiento y el ambiente diferencian a los gemelos"

ABC 5-5-2005 "Una tercera parte de los gemelos son diferentes por el envejecimiento y causas ambientales"
La Vanguardia 5-7-2005 "Tan iguales y tan distintos: Los científicos descubren por qué aparecen diferencias genéticas entre gemelos "
El Correo 5-7-2005 "Desvelan cómo los gemelos se van diferenciando con el paso del tiempo"
La Voz de Asturias 5-7-2005 "Un asturiano halla el origen de la diferencia física en gemelos"
Nature 4-7-2005 "Twins grow apart as they age"
Washington Post "Twin Data Highlight Genetic Changes: Minor Differences Increase With Age"
The New York Times 4-7-2005 "Explaining Differences in Twins"

on Fraga et al. (Nat Genet. 2005 Mar 13)
El Pais 14-3-2005 "Un estudio español revela una nueva vía en el origen de los tumores cancerosos"
El Periodico de Catalunya 14-3-2005 "Científicos españoles hallan otra vía del origen del cáncer"
La Vanguardia 14-3-2005 "Descubierto un fallo en la regulación de los genes que afecta al 90% de los cánceres"
ABC 14-3-2005 "Descubren un nuevo mecanismo celular capaz de generar cáncer"
Diario Médico 14-3-2005 "Un estudio español identifica una tercera vía que causa el cáncer, basada en la alteración de proteínas asociadas al ADN"
La Nueva España 14-3-2005 "Un investigador gijonés descubre un mecanismo celular clave en la lucha contra el cáncer"
La Nueva España 14-3-2005 "Un brillante currículum que incluye premios en la batalla contra los tumores"
La Voz de Asturias 14-3-2005 "Un gijonés abre una vía nueva contra el cáncer"
La Voz de Galicia 14-3-2005 "Un estudio español revela una nueva vía por la que se origina el cáncer"
El Correo 14-3-2005 "Científicos españoles vinculan el cáncer con la alteración de unas proteínas"
Diario de León 14-3-2005 "Un estudio español revela una nueva vía por la que se origina el cáncer"

 

Predoctoral Fellowship in the Cancer Epigenetics Group, CNIO

The Cancer Epigenetics Group is searching a candidate to perform his/her Ph.D during four years with the focus on cancer research of DNA methylation, DNA methylation binding proteins, histone modification, chromatin remodelling complexes and any epigenetic alteration for its possible diagnostic and therapeutic applications.

For more information and submission of CV write to mesteller@cnio.es

Representative publications:
Ballestar E, Paz MF, Valle L, Wei S, Fraga MF, Espada J, Cigudosa JC, Huang TH, Esteller M.
Methyl-CpG binding proteins identify novel sites of epigenetic inactivation in human cancer.
EMBO J. 2003 Dec 1;22(23):6335-45.

Paz MF, Wei S, Cigudosa JC, Rodriguez-Perales S, Peinado MA, Huang TH, Esteller M.
Genetic unmasking of epigenetically silenced tumor suppressor genes in colon cancer cells deficient in DNA methyltransferases.
Hum Mol Genet. 2003 Sep 1;12(17):2209-19. Epub 2003 Jul 15.

Paz MF, Fraga MF, Avila S, Guo M, Pollan M, Herman JG, Esteller M.
A systematic profile of DNA methylation in human cancer cell lines.
Cancer Res. 2003 Mar 1;63(5):1114-21.

Job Requirements:
Bachelors dDegree in any of the Biomedical Sciences, specially in biochemistry and molecular biology.
GPA of 2.5 or higher, preferred. (Please indicate GPA on CV).

Benefits:
Predoctoral fellowship for four years.
Incorporation in an acredited international research Centre.
Financial aid for English/Spanish lessons.

 

DNA Methylation. Approaches, Methods and Applications
Edited by Manel Esteller

CRC Press
List Price: $149.95
Cat. #: 2050
ISBN: 084932050X
Publication Date: 9/28/2004
Number of Pages: 240

- Discusses the impact of DNA methylation in human health and disease
- Includes concepts, experimental models, and clinical uses of demethylating agents
- Presents the most current research on the impact of DNA methylation in cancer
- Features the work of the foremost leaders in the field

A guide to understanding the complex regulatory roles of DNA methylation, this volume describes the relation that this biological mechanism has to gene silencing in disease and explores its promising role in treating cancer. DNA Methylation: Approaches, Methods and Applications describes the relation DNA methylation has to gene silencing in disease, and explores its promising role in treating cancer. The author considers research, clinical, and industry perspectives in this growing field, and by synthesizing previously scattered literature, he offers the subject's first organized and cohesive resource and bibliography.
The book is a state-of-the-art reference for understanding the role DNA methylation plays in human disease, particularly cancer. Written by leaders in the field, this exceptional compilation of articles outlines the best techniques to use when addressing questions concerning the cytosine methylation status of genomic DNA. It includes concepts, experimental models, and clinical uses of demethylating agents. The book provides a balance between articles clarifying methodological details and more general review chapters that offer broad biological perspectives on DNA methylation.
Covering fundamental theory, technologies, and applications, DNA Methylation: Approaches Methods, and Applications presents the most current research on using DNA methylation to decipher the pathways involved in human disease. This is an invaluable handbook for researchers and clinicians interested in genetics and molecular biology, particularly epigenetic therapies and gene silencing.

 

DNA Methylation, Epigenetics and Metastasis

Series: Cancer Metastasis - Biology and Treatment, Vol. 7
Esteller, Manel (Ed.)
2005, XI, 310 p., Hardcover
ISBN: 1-4020-3641-8
Not yet published
Prepublication price , valid until Aug 31, 2005: US$102.00

About this book
This book provides a broad and rich outline of the epigenetic mechanisms involved in cancer progression and the generation of metastasis. It describes the tumor suppressor genes undergoing transcriptional silencing by CpG island promoter hypermethylation in the different tumor types of the human anatomy and their association with tumoral behaviour. It also provides a comprehensive insightful look at the molecular players involved in DNA methylation, histone modification and chromatin remodelling complexes causing epigenetic lesions linked to the metastasic phenotypes. Finally, it explains how epigenetic lesions associated with cancer spreading can be targeted using new and potent chemotherapy drugs. The book is a state-of-the-art reference to all scientific researchers and clinicians interested in the understanding of the biological processes leading to tumor dissemination and to those that are keen to translate this knowledge to a better management of cancer patients. Each contributor is a specialist in their epigenetic area and their joint effort has created a unique view of the DNA methylation, histone and chromatin changes that define cancer metastasis.

 

Latest Publications

Ballestar E, Esteller M, Richardson BC.
The epigenetic face of systemic lupus erythematosus.
J Immunol. 2006 Jun 15;176(12):7143-7.

Agrelo R, Cheng WH, Setien F, Ropero S, Espada J, Fraga MF, Herranz M, Paz MF, Sanchez-Cespedes M, Artiga MJ, Guerrero D, Castells A, von Kobbe C, Bohr VA, Esteller M.
Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer.
Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8822-7.

Esteller M.
The necessity of a human epigenome project.
Carcinogenesis. 2006 Jun;27(6):1121-5.

Herranz M, Esteller M.
New therapeutic targets in cancer: the epigenetic connection.
Clin Transl Oncol. 2006 Apr;8(4):242-9.

Ropero S, Fraga MF, Ballestar E, Hamelin R, Yamamoto H, Boix-Chornet M, Caballero R, Alaminos M, Setien F, Paz MF, Herranz M, Palacios J, Arango D, Orntoft TF, Aaltonen LA, Schwartz S Jr, Esteller M.
A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition.
Nat Genet. 2006 May;38(5):566-9.

Esteller M.
CpG island methylation and histone modifications: biology and clinical significance.
Ernst Schering Res Found Workshop. 2006;(57):115-26. Review.

Boix-Chornet M, Fraga MF, Villar-Garea A, Caballero R, Espada J, Nunez A, Casado J, Largo C, Casal JI, Cigudosa JC, Franco L, Esteller M, Ballestar E.
Release of hypoacetylated and trimethylated histone H4 is an epigenetic marker of early apoptosis.
J Biol Chem. 2006 May 12;281(19):13540-7.

Esteller M.
Epigenetics provides a new generation of oncogenes and tumour-suppressor genes.
Br J Cancer. 2006 Jan 30;94(2):179-83. Review.

Herranz M, Martin-Caballero J, Fraga MF, Ruiz-Cabello J, Flores JM, Desco M, Marquez V, Esteller M.
The novel DNA methylation inhibitor zebularine is effective against the development of murine T-cell lymphoma.
Blood. 2006 Feb 1;107(3):1174-7.

Fraga MF, Esteller M.
Towards the human cancer epigenome: a first draft of histone modifications.
Cell Cycle. 2005 Oct;4(10):1377-81. Epub 2005 Oct 20. Review.

Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M.
Epigenetic differences arise during the lifetime of monozygotic twins.
Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9.

 


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