Epigenetic activation of SOX11 in lymphoid neoplasms by histone modifications.
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...
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2011
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oai:doaj.org-article:a2c641b7ae244f298e229b4d1dca17bd2021-11-18T06:51:13ZEpigenetic activation of SOX11 in lymphoid neoplasms by histone modifications.1932-620310.1371/journal.pone.0021382https://doaj.org/article/a2c641b7ae244f298e229b4d1dca17bd2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21738649/?tool=EBIhttps://doaj.org/toc/1932-6203Recent 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.Maria Carmela VeglianteCristina RoyoJara PalomeroItziar SalaverriaBalazs BalintIdoia Martín-GuerreroXabier AgirreAmaia LujambioJulia RichterSilvia Xargay-TorrentSilvia BeaLuis HernandezAnna EnjuanesMaría José CalasanzAndreas RosenwaldGerman OttJosé Roman-GomezFelipe ProsperManel EstellerPedro JaresReiner SiebertElias CampoJosé I Martín-SuberoVirginia AmadorPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 6, p e21382 (2011) |
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Medicine R Science Q Maria Carmela Vegliante Cristina Royo Jara Palomero Itziar Salaverria Balazs Balint Idoia Martín-Guerrero Xabier Agirre Amaia Lujambio Julia Richter Silvia Xargay-Torrent Silvia Bea Luis Hernandez Anna Enjuanes María José Calasanz Andreas Rosenwald German Ott José Roman-Gomez Felipe Prosper Manel Esteller Pedro Jares Reiner Siebert Elias Campo José I Martín-Subero Virginia Amador Epigenetic activation of SOX11 in lymphoid neoplasms by histone modifications. |
| description |
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. |
| format |
article |
| author |
Maria Carmela Vegliante Cristina Royo Jara Palomero Itziar Salaverria Balazs Balint Idoia Martín-Guerrero Xabier Agirre Amaia Lujambio Julia Richter Silvia Xargay-Torrent Silvia Bea Luis Hernandez Anna Enjuanes María José Calasanz Andreas Rosenwald German Ott José Roman-Gomez Felipe Prosper Manel Esteller Pedro Jares Reiner Siebert Elias Campo José I Martín-Subero Virginia Amador |
| author_facet |
Maria Carmela Vegliante Cristina Royo Jara Palomero Itziar Salaverria Balazs Balint Idoia Martín-Guerrero Xabier Agirre Amaia Lujambio Julia Richter Silvia Xargay-Torrent Silvia Bea Luis Hernandez Anna Enjuanes María José Calasanz Andreas Rosenwald German Ott José Roman-Gomez Felipe Prosper Manel Esteller Pedro Jares Reiner Siebert Elias Campo José I Martín-Subero Virginia Amador |
| author_sort |
Maria Carmela Vegliante |
| title |
Epigenetic activation of SOX11 in lymphoid neoplasms by histone modifications. |
| title_short |
Epigenetic activation of SOX11 in lymphoid neoplasms by histone modifications. |
| title_full |
Epigenetic activation of SOX11 in lymphoid neoplasms by histone modifications. |
| title_fullStr |
Epigenetic activation of SOX11 in lymphoid neoplasms by histone modifications. |
| title_full_unstemmed |
Epigenetic activation of SOX11 in lymphoid neoplasms by histone modifications. |
| title_sort |
epigenetic activation of sox11 in lymphoid neoplasms by histone modifications. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/a2c641b7ae244f298e229b4d1dca17bd |
| work_keys_str_mv |
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| _version_ |
1718424310113107968 |