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2011-06-27

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cc-by (c) Vegliante, M.C. et al., 2011
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/43784

Epigenetic Activation of SOX11 in Lymphoid Neoplasms by Histone Modifications

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http://dx.doi.org/10.1371/journal.pone.0021382

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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.

Matèries

Limfomes, Histones, Carcinogènesi

Matèries (anglès)

Lymphomas, Histones, Carcinogenesis

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Articles publicats en revistes (Fonaments Clínics)

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VEGLIANTE, Maria carmela, ROYO MORENO, Cristina, PALOMERO, Jara, SALAVERRIA FRIGOLA, Itziar, BALINT, Balazs, MARTÍN GUERRERO, Idoia, AGIRRE, Xabier, LUJAMBIO, Amaia, RICHTER, Julia, XARGAY I TORRENT, Sílvia, BEÀ BOBET, Sílvia m., HERNÁNDEZ, Luis, ENJUANES, Anna, CALASANZ, María josé, ROSENWALD, Andreas, CAMPO GÜERRI, Elias, ROMÁN-GÓMEZ, José, PROSPER, Felipe, ESTELLER, Manel, JARES GERBOLES, Pedro. Epigenetic Activation of SOX11 in Lymphoid Neoplasms by Histone Modifications. _PLoS One_. 2011. Vol. 6, núm. 6, pàgs. e21382. [consulta: 14 de abril de 2026]. ISSN: 1932-6203. [Disponible a: https://hdl.handle.net/2445/43784]

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