TY  - JOUR
A1  - Carmela Vegliante, Maria
A1  - Royo, Cristina
A1  - Palomero, Jara
A1  - Salaverria, Itziar
A1  - Balint, Balazs
A1  - Martin-Guerrero, Idoia
A1  - Agirre, Xabier
A1  - Lujambio, Amaia
A1  - Richter, Julia
A1  - Xargay-Torrent, Silvia
A1  - Bea, Silvia
A1  - Hernandez, Luis
A1  - Enjuanes, Anna
A1  - Jose Calasanz, Maria
A1  - Rosenwald, Andreas
A1  - Ott, German
A1  - Roman-Gomez, Jose
A1  - Prosper, Felipe
A1  - Esteller, Manel
A1  - Jares, Pedro
A1  - Siebert, Reiner
A1  - Campo, Elias
A1  - Martin-Subero, Jose I.
A1  - Amador, Virginia
T1  - Epigenetic Activation of SOX11 in Lymphoid Neoplasms by Histone Modifications
JF  - PLoS ONE
N2  - 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.
KW  - Mantle cell lymphoma
KW  - Defined burkitts lymphoma
KW  - Transcription-factor
KW  - Gene-expression
KW  - High-resolution
KW  - DNA methylation
KW  - Nuclear expression
KW  - Cancer
KW  - Microarray
KW  - Survival
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135325
VL  - 6
IS  - 6
ER  -