Epigenetic activation of SOX11 in lymphoid neoplasms by histone modifications
| Autor: | Anna Enjuanes, Felipe Prosper, Amaia Lujambio, Itziar Salaverria, Xabier Agirre, Manel Esteller, Jara Palomero, Elias Campo, Silvia Xargay-Torrent, Cristina Royo, Virginia Amador, Andreas Rosenwald, José I. Martín-Subero, Sílvia Beà, Reiner Siebert, Idoia Martin-Guerrero, Balázs Bálint, German Ott, Jose Roman-Gomez, Maria Carmela Vegliante, Julia Richter, Luis Hernández, Pedro Jares, María José Calasanz |
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| Přispěvatelé: | Universitat de Barcelona |
| Rok vydání: | 2011 |
| Předmět: |
Limfomes
Chromatin Immunoprecipitation Lymphoma medicine.drug_class Carcinogenesis Science Blotting Western Biology In Vitro Techniques Epigenesis Genetic SOXC Transcription Factors Hematologic Cancers and Related Disorders Histones Cell Line Tumor Leukemias medicine Genetics Humans Carcinogènesi Cancer epigenetics Epigenetics ddc:610 Oligonucleotide Array Sequence Analysis Multidisciplinary Reverse Transcriptase Polymerase Chain Reaction Histone deacetylase inhibitor Cancers and Neoplasms Hematology DNA Methylation DNA Methylation/drug effects Histone Deacetylase Inhibitors Histone Oncology DNA methylation Cancer research biology.protein H3K4me3 Medicine Lymphomas Gene expression Stem cell DNA modification Histone modification Chromatin immunoprecipitation Research Article |
| Zdroj: | Dadun. Depósito Académico Digital de la Universidad de Navarra instname Dipòsit Digital de la UB Universidad de Barcelona PLoS ONE Recercat. Dipósit de la Recerca de Catalunya PLoS ONE, Vol 6, Iss 6, p e21382 (2011) |
| Popis: | Recent studies have shown aberrant expression of SOX11 in various types of aggressive B-cell neoplasms. To elucidate the molecular mechanisms leading to such deregulation, we performed a comprehensive SOX11 gene expression and epigenetic study in stem cells, normal hematopoietic cells and different lymphoid neoplasms. We observed that SOX11 expression is associated with unmethylated DNA and presence of activating histone marks (H3K9/14Ac and H3K4me3) in embryonic stem cells and some aggressive B-cell neoplasms. In contrast, adult stem cells, normal hematopoietic cells and other lymphoid neoplasms do not express SOX11. Such repression was associated with silencing histone marks H3K9me2 and H3K27me3. The SOX11 promoter of non-malignant cells was consistently unmethylated whereas lymphoid neoplasms with silenced SOX11 tended to acquire DNA hypermethylation. SOX11 silencing in cell lines was reversed by the histone deacetylase inhibitor SAHA but not by the DNA methyltransferase inhibitor AZA. These data indicate that, although DNA hypermethylation of SOX11 is frequent in lymphoid neoplasms, it seems to be functionally inert, as SOX11 is already silenced in the hematopoietic system. In contrast, the pathogenic role of SOX11 is associated with its de novo expression in some aggressive lymphoid malignancies, which is mediated by a shift from inactivating to activating histone modifications. |
| Databáze: | OpenAIRE |
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