Manel Esteller

Frequent loss of endothelin-3 (EDN3) expression due to epigenetic inactivation in human breast cancer (2009)

Wiesmann, Frank, Veeck, Jürgen, Galm, Oliver, Hartmann, Arndt, Esteller, Manel, Knüchel, Ruth, ...

Abstract Introduction Endothelin (EDN) signalling plays a crucial role in cell differentiation, proliferation and migration processes. There is compelling evidence that altered EDN signalling is...

A Role for RNAi in the Selective Correction of DNA Methylation Defects (2009)

Teixeira, Felipe Karam, Heredia, Fabiana, Sarazin, Alexis, Roudier, François, Boccara, Martine, Ciaudo, Constance, ...

8 pages, 4 figures.-- PMID: 19179494 [PubMed].-- GEO accession number for small RNA sequences: GSE13419.

The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer (2009)

Fernandez, Agustin F., Rosales, Cecilia, Lopez-Nieva, Pilar, Graña, Osvaldo, Ballestar, Esteban, Ropero, Santiago, ...

The natural history of cancers associated with virus exposure is intriguing, since only a minority of human tissues infected with these viruses inevitably progress to cancer. However, the molecular...

The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA (2009)

López De Silanes, Isabel, Gorospe, Myriam, Taniguchi, Hiroaki, Abdelmohsen, Kotb, Srikantan, Subramanya, Alaminos, Miguel, ...

The molecular basis underlying the aberrant DNA-methylation patterns in human cancer is largely unknown. Altered DNA methyltransferase (DNMT) activity is believed to contribute, as DNMT expression...

Loss of the glycine N-methyltransferase gene leads to steatosis and hepatocellular carcinoma in mice (2008)

Martínez-Chantar, M. Luz, Vázquez-Chantada, Mercedes, Ariz, Usue, Martínez, Nuria, Varela, Marta, Luka, Zigmund, ...

Glycine N-methyltransferase (GNMT) is the main enzyme responsible for catabolism of excess hepatic S-adenosylmethionine (SAMe). GNMT is absent in hepatocellular carcinoma (HCC), messenger RNA (mRNA)...

The Wnt antagonist DICKKOPF-1 gene is induced by 1{alpha},25-dihydroxyvitamin D3 associated to the differentiation of human colon cancer cells (2007)

Aguilera, Oscar, Peña, Cristina, García, José Miguel, Larriba, María Jesús, Ordóñez-Morán, Paloma, Navarro, Diego, ...

The Wnt–β-catenin pathway is aberrantly activated in most colon cancers. DICKKOPF-1 (DKK-1) gene encodes an extracellular Wnt inhibitor that blocks the formation of signalling receptor complexes...

Epigenetic gene silencing in cancer: the DNA hypermethylome (2007)

Esteller, Manel

Epigenetic gene inactivation in transformed cells involves many ‘belts of silencing’. One of the best-known lesions of the malignant cell is the transcriptional repression of tumor-suppressor...

Mutator pathways unleashed by epigenetic silencing in human cancer (2007)

Jacinto, Filipe V., Esteller, Manel

Human cancers exhibit genomic instability and an increased mutation rate due to underlying defects in DNA repair genes. Hypermethylation of CpG islands in gene promoter regions is an important...

CpG island promoter hypermethylation of the pro-apoptotic gene caspase-8 is a common hallmark of relapsed glioblastoma multiforme (2007)

Martinez, Ramon, Setien, Fernando, Voelter, Christiane, Casado, Sara, Quesada, Maria P., Schackert, Gabriele, ...

Glioblastoma multiforme (GBM) is an incurable malignancy with inherent tendency to recur. In this study, we have comparatively analyzed the epigenetic profile of 32 paired tumor samples of relapsed...

Epigenetic disruption of ribosomal RNA genes and nucleolar architecture in DNA methyltransferase 1 (Dnmt1) deficient cells (2007)

Espada, Jesús, Ballestar, Esteban, Santoro, Raffaella, Fraga, Mario F., Villar-Garea, Ana, Németh, Attila, ...

The nucleolus is the site of ribosome synthesis in the nucleus, whose integrity is essential. Epigenetic mechanisms are thought to regulate the activity of the ribosomal RNA (rRNA) gene copies, which...

Epigenetic disruption of ribosomal RNA genes and nucleolar architecture in DNA methyltransferase 1 (Dnmt1) deficient cells (2007)

Espada, Jesús, Ballestar, Esteban, Santoro, Raffaella, Fraga, Mario F., Villar-Garea, Ana, Németh, Attila, ...

The nucleolus is the site of ribosome synthesis in the nucleus, whose integrity is essential. Epigenetic mechanisms are thought to regulate the activity of the ribosomal RNA (rRNA) gene copies, which...

CpG island promoter hypermethylation of the pro-apoptotic gene caspase-8 is a common hallmark of relapsed glioblastoma multiforme (2007)

Martinez, Ramon, Setien, Fernando, Voelter, Christiane, Casado, Sara, Quesada, Maria Paz, Schackert, Gabriele, ...

Glioblastoma multiforme (GBM) is an incurable malignancy with inherent tendency to recur. In this study we have comparatively analyzed the epigenetic profile of thirty-two paired tumor samples of...

The Polycomb group protein EZH2 directly controls DNA methylation (2006)

Brenner, Carmen, Deplus, Rachel, Blanchon, Loïc, Fraga, Mario, Didelot, Céline, ...

The establishment and maintenance of epigenetic gene silencing is fundamental to cell determination and function. The essential epigenetic systems involved in heritable repression of gene activity...

The necessity of a human epigenome project (2006)

Esteller, Manel

Epigenetics is one of the hottest topics in cancer research. We know that human tumors undergo a major disruption of their DNA methylation and histone modification patterns. The aberrant epigenetic...

Genetic variants in epigenetic genes and breast cancer risk (2006)

Cebrian, Arancha, Pharoah, Paul D., Ahmed, Shahana, Ropero, Santiago, Fraga, Mario F., Smith, Paula L., ...

Epigenetic events, resulting changes in gene expression capacity, are important in tumour progression, and variation in genes involved in epigenetic mechanisms might therefore be important in cancer...

The necessity of a Human Epigenome Project (2006)

Esteller, Manel

Epigenetics is one of the hottest topics in cancer research. We know that human tumors undergo a major disruption of their DNA methylation and histone modification patterns. The aberrant epigenetic...

The necessity of a Human Epigenome Project (2006)

Esteller, Manel

Epigenetics is one of the hottest topics in cancer research. We know that human tumors undergo a major disruption of their DNA methylation and histone modification patterns. The aberrant epigenetic...

Genetic variants in epigenetic genes and breast cancer risk (2006)

Cebrian, Arancha, Pharoah, Paul D., Ahmed, Shahana, Ropero, Santiago, Fraga, Mario F., Smith, Paula L., ...

Epigenetic events, resulting changes in gene expression capacity, are important in tumour progression, and variation in genes involved in epigenetic mechanisms might therefore be important in cancer...

The loss of NKX3.1 expression in testicular – and prostate – cancers is not caused by promoter hypermethylation (2005)

Lind, Guro E, Skotheim, Rolf I, Fraga, Mario F, Abeler, Vera M, Henrique, Rui, Saatcioglu, Fahri, ...

Abstract Background Recent studies have demonstrated that the NKX3.1 protein is commonly down-regulated in testicular germ cell tumors (TGCTs) and prostate carcinomas. The homeobox gene NKX3.1 maps...

Differential DNA hypermethylation and hypomethylation signatures in colorectal cancer (2005)

Frigola, Jordi, Solé, Xavier, Paz, Maria F., Moreno, Victor, Esteller, Manel, Capellà, Gabriel, ...

Cancer cells are characterized by a generalized disruption of the DNA methylation pattern involving an overall decrease in the level of 5-methylcytosine together with regional hypermethylation of...

Multiple markers for melanoma progression regulated by DNA methylation: insights from transcriptomic studies (2005)

Gallagher, William M., Bergin, Orla E., Rafferty, Mairin, Kelly, Zoë D., Nolan, Ilse-Maria, Fox, Edward J.P., ...

The incidence of melanoma is increasing rapidly, with advanced lesions generally failing to respond to conventional chemotherapy. Here, we utilized DNA microarray-based gene expression profiling...

Multiple markers for melanoma progression regulated by DNA methylation: insights from transcriptomic studies (2005)

Gallagher, William M., Bergin, Orla E., Rafferty, Mairin, Kelly, Zoë D., Nolan, Ilse-Maria, Fox, Edward J. P., ...

The incidence of melanoma is increasing rapidly, with advanced lesions generally failing to respond to conventional chemotherapy. Here, we utilized DNA microarray-based gene expression profiling...

Transcriptional targets of the chromatin-remodelling factor SMARCA4/BRG1 in lung cancer cells (2005)

Medina, Pedro P., Carretero, Julian, Ballestar, Esteban, Angulo, Barbara, Lopez-Rios, Fernando, Esteller, Manel, ...

BRG1, also called SMARCA4, is the catalytic subunit of the SWI/SNF chromatin-remodelling complex and influences transcriptional regulation by disrupting histone–DNA contacts in an ATP-dependent...

Transcriptional targets of the chromatin-remodelling factor SMARCA4/BRG1 in lung cancer cells (2005)

Medina, Pedro P., Carretero, Julian, Ballestar, Esteban, Angulo, Barbara, Lopez-Rios, Fernando, Esteller, Manel, ...

BRG1, also called SMARCA4, is the catalytic subunit of the SWI/SNF chromatin-remodelling complex and influences transcriptional regulation by disrupting histone-DNA contacts in an ATP-dependent...

A CpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines (2004)

Lind, Guro E, Thorstensen, Lin, Løvig, Tone, Meling, Gunn I, Hamelin, Richard, Rognum, Torleiv O, ...

Abstract Background Tumor cell lines are commonly used as experimental tools in cancer research, but their relevance for the in vivo situation is debated. In a series of 11 microsatellite stable...

A CpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines. (2004)

Lind, Guro, Thorstensen, Lin, Løvig, Tone, Meling, Gunn, Hamelin, Richard, Rognum, Torleiv, ...

BACKGROUND: Tumor cell lines are commonly used as experimental tools in cancer research, but their relevance for the in vivo situation is debated. In a series of 11 microsatellite stable (MSS) and 9...

A CpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines. (2004)

Lind, Guro, Thorstensen, Lin, Løvig, Tone, Meling, Gunn, Hamelin, Richard, Rognum, Torleiv, ...

BACKGROUND: Tumor cell lines are commonly used as experimental tools in cancer research, but their relevance for the in vivo situation is debated. In a series of 11 microsatellite stable (MSS) and 9...

A CpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines. (2004)

Lind, Guro, Thorstensen, Lin, Løvig, Tone, Meling, Gunn, Hamelin, Richard, Rognum, Torleiv, ...

BACKGROUND: Tumor cell lines are commonly used as experimental tools in cancer research, but their relevance for the in vivo situation is debated. In a series of 11 microsatellite stable (MSS) and 9...

A CpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines. (2004)

Lind, Guro, Thorstensen, Lin, Løvig, Tone, Meling, Gunn, Hamelin, Richard, Rognum, Torleiv, ...

BACKGROUND: Tumor cell lines are commonly used as experimental tools in cancer research, but their relevance for the in vivo situation is debated. In a series of 11 microsatellite stable (MSS) and 9...

Epigenetic loss of the familial tumor-suppressor gene exostosin-1 (EXT1) disrupts heparan sulfate synthesis in cancer cells (2004)

Ropero, Santiago, Setien, Fernando, Espada, Jesus, Fraga, Mario F., Herranz, Michel, Asp, Julia, ...

Germline mutations in the Exostoses-1 gene (EXT1) are found in hereditary multiple exostoses (HME) syndrome, which is characterized by the formation of osteochondromas and an increased risk of...

Differential DNA hypermethylation and hypomethylation signatures in colorectal cancer (2004)

Frigola, Jordi, Solé, Xavier, Paz, Maria F., Moreno, Victor, Esteller, Manel, Capellà, Gabriel, ...

Cancer cells are characterized by a generalized disruption of the DNA methylation pattern involving an overall decrease in the level of 5-methylcytosine together with regional hypermethylation of...

Clustering of Gene Hypermethylation Associated With Clinical Risk Groups in Neuroblastoma (2004)

Alaminos, Miguel, Davalos, Veronica, Cheung, Nai-Kong V., Gerald, William L., Esteller, Manel

Background: Neuroblastoma is the most common extracranial solid malignancy in infancy and childhood, but the biological factors involved in its development and progression are still unclear....

Epigenetic loss of the familial tumor-suppressor gene exostosin-1 (EXT1) disrupts heparan sulfate synthesis in cancer cells (2004)

Ropero, Santiago, Setien, Fernando, Espada, Jesus, Fraga, Mario F., Herranz, Michel, Asp, Julia, ...

Germline mutations in the Exostoses-1 gene (EXT1) are found in hereditary multiple exostoses syndrome, which is characterized by the formation of osteochondromas and an increased risk of...

Epigenetic loss of the familial tumor-suppressor gene exostosin-1 (EXT1) disrupts heparan sulfate synthesis in cancer cells (2004)

Ropero, Santiago, Setien, Fernando, Espada, Jesus, Fraga, Mario F., Herranz, Michel, Asp, Julia, ...

Germline mutations in the Exostoses-1 gene (EXT1) are found in hereditary multiple exostoses (HME) syndrome, which is characterized by the formation of osteochondromas and an increased risk of...

Differential DNA hypermethylation and hypomethylation signatures in colorectal cancer (2004)

Frigola, Jordi, Solé, Xavier, Paz, Maria F., Moreno, Victor, Esteller, Manel, Capellà, Gabriel, ...

Cancer cells are characterized by a generalized disruption of the DNA methylation pattern involving an overall decrease in the level of 5-methylcytosine together with regional hypermethylation of...

Genetic Unmasking of Epigenetically Silenced Tumor Suppressor Genes in Colon Cancer Cells Deficient in DNA Methyltransferases (2003)

Paz, Maria F., Wei, Susan, Cigudosa, Juan C., Rodriguez-Perales, Sandra, Peinado, Miguel A., Huang, Tim Hui-Ming, ...

Hypermethylation-associated silencing of the CpG islands of tumor suppressor genes is a common hallmark of human cancer. Here we report a functional search for hypermethylated CpG islands using the...

Genetic unmasking of epigenetically silenced tumor suppressor genes in colon cancer cells deficient in DNA methyltransferases (2003)

Paz, Maria F., Wei, Susan, Cigudosa, Juan C., Rodriguez-Perales, Sandra, Peinado, Miguel A., Huang, Tim Hui-Ming, ...

Hypermethylation associated silencing of the CpG islands of tumor suppressor genes is a common hallmark of human cancer. Here we report a functional search for hypermethylated CpG islands using the...

The affinity of different MBD proteins for a specific methylated locus depends on their intrinsic binding properties (2003)

Fraga, Mario F., Ballestar, Esteban, Montoya, Guillermo, Taysavang, Panya, Wade, Paul A., Esteller, Manel

The methyl‐CpG binding domain (MBD) family of proteins was defined based on sequence similarity in their DNA binding domains. In light of their high degree of conservation, it is of inherent...

Genetic Unmasking of Epigenetically Silenced Tumor Suppressor Genes in Colon Cancer Cells Deficient in DNA Methyltransferases (2003)

Paz, Maria F., Wei, Susan, Cigudosa, Juan C., Rodriguez-Perales, Sandra, Peinado, Miguel A., Huang, Tim Hui-Ming, ...

Hypermethylation-associated silencing of the CpG islands of tumor suppressor genes is a common hallmark of human cancer. Here we report a functional search for hypermethylated CpG islands using the...

The impact of chromatin in human cancer: linking DNA methylation to gene silencing (2002)

Ballestar, Esteban, Esteller, Manel

For decades, chromatin was considered to be an inert structure whose only role was the compacting and confining of DNA inside the eukaryotic nucleus. However, tremendous progress in this field over...

Hypermethylation of the DNA Repair Gene O6-Methylguanine DNA Methyltransferase and Survival of Patients With Diffuse Large B-Cell Lymphoma (2002)

Esteller, Manel, Gaidano, Gianluca, Goodman, Steven N., Zagonel, Vittorina, Capello, Daniela, Botto, Barbara, ...

Background: The gene encoding the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) is transcriptionally silenced by promoter hypermethylation in several human cancers, including...

Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer (2001)

Baylin, Stephen B., Esteller, Manel, Rountree, Michael R., Bachman, Kurtis E., Schuebel, Kornel, Herman, James G.

Gene function in cancer can be disrupted either through genetic alterations, which directly mutate or delete genes, or epigenetic alterations, which alter the heritable state of gene expression. The...

Promoter Hypermethylation and BRCA1 Inactivation in Sporadic Breast and Ovarian Tumors (2000)

Esteller, Manel, Silva, Jose Maria, Dominguez, Gemma, Bonilla, Felix, Matias-Guiu, Xavier, Lerma, Enrique, ...

Background: Inherited mutations in the BRCA1 gene may be responsible for almost half of inherited breast carcinomas. However, somatic (acquired) mutations in BRCA1 have not been reported, despite...

Molecular Detection of Tumor Cells in Bronchoalveolar Lavage Fluid From Patients With Early Stage Lung Cancer (1999)

Ahrendt, Steven A., Chow, John T., Xu, Li-Hua, Yang, Stephen C., Eisenberger, Claus F., Esteller, Manel, ...

BACKGROUND: Conventional cytologic analysis of sputum is an insensitive test for the diagnosis of non-small-cell lung cancer (NSCLC). We have recently demonstrated that polymerase chain reaction...

Allele-specific histone lysine methylation marks regulatory regions at imprinted mouse genes

Fournier, Cécile, Goto, Yuji, Ballestar, Esteban, Delaval, Katia, Hever, Ann M., Esteller, Manel, ...

In different eukaryotic model systems, chromatin and gene expression are modulated by post-translational modification of histone tails. In this in vivo study, histone methylation and acetylation are...

The affinity of different MBD proteins for a specific methylated locus depends on their intrinsic binding properties

Fraga, Mario F., Ballestar, Esteban, Montoya, Guillermo, Taysavang, Panya, Wade, Paul A., Esteller, Manel

The methyl-CpG binding domain (MBD) family of proteins was defined based on sequence similarity in their DNA binding domains. In light of their high degree of conservation, it is of inherent interest...

GATA-4 and GATA-5 Transcription Factor Genes and Potential Downstream Antitumor Target Genes Are Epigenetically Silenced in Colorectal and Gastric Cancer

Akiyama, Yoshimitsu, Watkins, Neil, Suzuki, Hiromu, Jair, Kam-Wing, Van Engeland, Manon, Esteller, Manel, ...

The GATA family of transcription factors participates in gastrointestinal (GI) development. Increases in GATA-4 and -5 expression occur in differentiation and GATA-6 expression in proliferation in...

Methyl-CpG binding proteins identify novel sites of epigenetic inactivation in human cancer

Ballestar, Esteban, Paz, Maria F., Valle, Laura, Wei, Susan, Fraga, Mario F., Espada, Jesus, ...

Methyl-CpG binding proteins (MBDs) mediate histone deacetylase-dependent transcriptional silencing at methylated CpG islands. Using chromatin immunoprecitation (ChIP) we have found that gene-specific...

Snail Mediates E-Cadherin Repression by the Recruitment of the Sin3A/Histone Deacetylase 1 (HDAC1)/HDAC2 Complex

Peinado, Hector, Ballestar, Esteban, Esteller, Manel, Cano, Amparo

The transcription factor Snail has been described as a direct repressor of E-cadherin expression during development and carcinogenesis; however, the specific mechanisms involved in this process...

E47 phosphorylation by p38 MAPK promotes MyoD/E47 association and muscle-specific gene transcription

Lluís, Frederic, Ballestar, Esteban, Suelves, Mònica, Esteller, Manel, Muñoz-Cánoves, Pura

Selective recognition of the E-box sequences on muscle gene promoters by heterodimers of myogenic basic helix–loop–helix (bHLH) transcription factors, such as MyoD, with the ubiquitous bHLH...

Epigenetic differences arise during the lifetime of monozygotic twins

Fraga, Mario F., Ballestar, Esteban, Paz, Maria F., Ropero, Santiago, Setien, Fernando, Ballestar, Maria L., ...

Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to...

How epigenetics integrates nuclear functions

Esteller, Manel, Almouzni, Geneviève

Workshop on Epigenetics and Chromatin: Transcriptional Regulation and Beyond

Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer

Agrelo, Ruben, Cheng, Wen-Hsing, Setien, Fernando, Ropero, Santiago, Espada, Jesus, Fraga, Mario F., ...

Werner syndrome (WS) is an inherited disorder characterized by premature onset of aging, genomic instability, and increased cancer incidence. The disease is caused by loss of function mutations of...

Allele-specific histone lysine methylation marks regulatory regions at imprinted mouse genes

Fournier, Cécile, Goto, Yuji, Ballestar, Esteban, Delaval, Katia, Hever, Ann M., Esteller, Manel, ...

In different eukaryotic model systems, chromatin and gene expression are modulated by post-translational modification of histone tails. In this in vivo study, histone methylation and acetylation are...

The affinity of different MBD proteins for a specific methylated locus depends on their intrinsic binding properties

Fraga, Mario F., Ballestar, Esteban, Montoya, Guillermo, Taysavang, Panya, Wade, Paul A., Esteller, Manel

The methyl-CpG binding domain (MBD) family of proteins was defined based on sequence similarity in their DNA binding domains. In light of their high degree of conservation, it is of inherent interest...

GATA-4 and GATA-5 Transcription Factor Genes and Potential Downstream Antitumor Target Genes Are Epigenetically Silenced in Colorectal and Gastric Cancer

Akiyama, Yoshimitsu, Watkins, Neil, Suzuki, Hiromu, Jair, Kam-Wing, Van Engeland, Manon, Esteller, Manel, ...

The GATA family of transcription factors participates in gastrointestinal (GI) development. Increases in GATA-4 and -5 expression occur in differentiation and GATA-6 expression in proliferation in...

Methyl-CpG binding proteins identify novel sites of epigenetic inactivation in human cancer

Ballestar, Esteban, Paz, Maria F., Valle, Laura, Wei, Susan, Fraga, Mario F., Espada, Jesus, ...

Methyl-CpG binding proteins (MBDs) mediate histone deacetylase-dependent transcriptional silencing at methylated CpG islands. Using chromatin immunoprecitation (ChIP) we have found that gene-specific...

Snail Mediates E-Cadherin Repression by the Recruitment of the Sin3A/Histone Deacetylase 1 (HDAC1)/HDAC2 Complex

Peinado, Hector, Ballestar, Esteban, Esteller, Manel, Cano, Amparo

The transcription factor Snail has been described as a direct repressor of E-cadherin expression during development and carcinogenesis; however, the specific mechanisms involved in this process...

E47 phosphorylation by p38 MAPK promotes MyoD/E47 association and muscle-specific gene transcription

Lluís, Frederic, Ballestar, Esteban, Suelves, Mònica, Esteller, Manel, Muñoz-Cánoves, Pura

Selective recognition of the E-box sequences on muscle gene promoters by heterodimers of myogenic basic helix–loop–helix (bHLH) transcription factors, such as MyoD, with the ubiquitous bHLH...

Epigenetic differences arise during the lifetime of monozygotic twins

Fraga, Mario F., Ballestar, Esteban, Paz, Maria F., Ropero, Santiago, Setien, Fernando, Ballestar, Maria L., ...

Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to...

How epigenetics integrates nuclear functions

Esteller, Manel, Almouzni, Geneviève

Workshop on Epigenetics and Chromatin: Transcriptional Regulation and Beyond

Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer

Agrelo, Ruben, Cheng, Wen-Hsing, Setien, Fernando, Ropero, Santiago, Espada, Jesus, Fraga, Mario F., ...

Werner syndrome (WS) is an inherited disorder characterized by premature onset of aging, genomic instability, and increased cancer incidence. The disease is caused by loss of function mutations of...

Epigenetic disruption of ribosomal RNA genes and nucleolar architecture in DNA methyltransferase 1 (Dnmt1) deficient cells

Espada, Jesús, Ballestar, Esteban, Santoro, Raffaella, Fraga, Mario F., Villar-Garea, Ana, Németh, Attila, ...

The nucleolus is the site of ribosome synthesis in the nucleus, whose integrity is essential. Epigenetic mechanisms are thought to regulate the activity of the ribosomal RNA (rRNA) gene copies, which...

hMLH1 Promoter Hypermethylation Is an Early Event in Human Endometrial Tumorigenesis

Esteller, Manel, Catasus, Lluis, Matias-Guiu, Xavier, Mutter, George L., Prat, Jaime, Baylin, Steve B., ...

It has recently been suggested that silencing of the hMLH1 gene by promoter hypermethylation is the mechanism underlying the presence of the microsatellite instability (MSI) phenotype in sporadic...

Molecular Analysis of a Multistep Lung Cancer Model Induced by Chronic Inflammation Reveals Epigenetic Regulation of p16 and Activation of the DNA Damage Response Pathway12

Blanco, David, Vicent, Silvestre, Fraga, Mario F, Fernandez-Garcia, Ignacio, Freire, Javier, Lujambio, Amaia, ...

The molecular hallmarks of inflammation-mediated lung carcinogenesis have not been fully clarified, mainly due to the scarcity of appropriate animal models. We have used a silica-induced multistep...

WNT10B Functional Dualism: β-Catenin/Tcf-dependent Growth Promotion or Independent Suppression with Deregulated Expression in Cancer

Yoshikawa, Hirohide, Matsubara, Kenichi, Zhou, Xiaoling, Okamura, Shu, Kubo, Takahiko, Murase, Yaeko, ...

We found aberrant DNA methylation of the WNT10B promoter region in 46% of primary hepatocellular carcinoma (HCC) and 15% of colon cancer samples. Three of 10 HCC and one of two colon cancer cell...

Genetic analysis of p38 MAP kinases in myogenesis: fundamental role of p38α in abrogating myoblast proliferation

Perdiguero, Eusebio, Ruiz-Bonilla, Vanessa, Gresh, Lionel, Hui, Lijian, Ballestar, Esteban, Sousa-Victor, Pedro, ...

The p38 mitogen-activated protein kinase (MAPK) pathway plays a critical role in skeletal muscle differentiation. However, the relative contribution of the four p38 MAPKs (p38α, p38β, p38γ and...

Cancer Genes Hypermethylated in Human Embryonic Stem Cells

Calvanese, Vincenzo, Horrillo, Angelica, Hmadcha, Abdelkrim, Suarez-Álvarez, Beatriz, Fernandez, Agustín F., Lara, Ester, ...

Developmental genes are silenced in embryonic stem cells by a bivalent histone-based chromatin mark. It has been proposed that this mark also confers a predisposition to aberrant DNA promoter...

Promoter DNA Hypermethylation and Gene Repression in Undifferentiated Arabidopsis Cells

Berdasco, María, Alcázar, Rubén, García-Ortiz, María Victoria, Ballestar, Esteban, Fernández, Agustín F., Roldán-Arjona, Teresa, ...

Maintaining and acquiring the pluripotent cell state in plants is critical to tissue regeneration and vegetative multiplication. Histone-based epigenetic mechanisms are important for regulating this...

A microRNA DNA methylation signature for human cancer metastasis

Lujambio, Amaia, Calin, George A., Villanueva, Alberto, Ropero, Santiago, Sánchez-Céspedes, Montserrat, Blanco, David, ...

MicroRNAs (miRNAs) are small, noncoding RNAs that can contribute to cancer development and progression by acting as oncogenes or tumor suppressor genes. Recent studies have also linked different sets...

The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA

López De Silanes, Isabel, Gorospe, Myriam, Taniguchi, Hiroaki, Abdelmohsen, Kotb, Srikantan, Subramanya, Alaminos, Miguel, ...

The molecular basis underlying the aberrant DNA-methylation patterns in human cancer is largely unknown. Altered DNA methyltransferase (DNMT) activity is believed to contribute, as DNMT expression...

The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer

Fernandez, Agustin F., Rosales, Cecilia, Lopez-Nieva, Pilar, Graña, Osvaldo, Ballestar, Esteban, Ropero, Santiago, ...

The natural history of cancers associated with virus exposure is intriguing, since only a minority of human tissues infected with these viruses inevitably progress to cancer. However, the molecular...

CSL–MAML-dependent Notch1 signaling controls T lineage–specific IL-7Rα gene expression in early human thymopoiesis and leukemia

González-García, Sara, García-Peydró, Marina, Martín-Gayo, Enrique, Ballestar, Esteban, Esteller, Manel, Bornstein, Rafael, ...

Notch1 activation is essential for T-lineage specification of lymphomyeloid progenitors seeding the thymus. Progression along the T cell lineage further requires cooperative signaling provided by the...