Epigenetic Activation of SOX11 in Lymphoid Neoplasms by Histone Modifications

被引：41

作者：

Carmela Vegliante, Maria ^{[1
]}

Royo, Cristina ^{[1
]}

Palomero, Jara ^{[1
]}

Salaverria, Itziar ^{[2
,3
]}

Balint, Balazs ^{[4
]}

Martin-Guerrero, Idoia ^{[2
,3
]}

Agirre, Xabier ^{[5
,6
]}

Lujambio, Amaia ^{[4
]}

Richter, Julia ^{[2
,3
]}

Xargay-Torrent, Silvia ^{[1
]}

Bea, Silvia ^{[1
]}

Hernandez, Luis ^{[1
]}

Enjuanes, Anna ^{[1
]}

Jose Calasanz, Maria ^{[7
]}

Rosenwald, Andreas ^{[8
]}

Ott, German ^{[9
,10
]}

Roman-Gomez, Jose ^{[11
]}

Prosper, Felipe ^{[5
,6
]}

Esteller, Manel ^{[4
]}

Jares, Pedro ^{[1
]}

Siebert, Reiner ^{[2
,3
]}

Campo, Elias ^{[1
,12
]}

Martin-Subero, Jose I. ^{[12
]}

Amador, Virginia ^{[1
]}

机构：

[1] Univ Barcelona, Hematopathol Sect, Pathol Lab, Hosp Clin,Inst Invest Biomed August Pi & Sunyer I, Barcelona, Spain

[2] Univ Kiel, Inst Human Genet, Kiel, Germany

[3] Univ Hosp Schleswig Holstein, Kiel, Germany

[4] Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Barcelona, Spain

[5] Univ Navarra, Fdn Appl Med Res, Clin Univ Navarra, Hematol Serv, E-31080 Pamplona, Spain

[6] Univ Navarra, Fdn Appl Med Res, Clin Univ Navarra, Area Cell Therapy, E-31080 Pamplona, Spain

[7] Univ Navarra, Dept Genet, E-31080 Pamplona, Spain

[8] Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany

[9] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany

[10] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany

[11] Reina Sofia Hosp, Dept Hematol, Cordoba, Spain

[12] Univ Barcelona, Dept Anat Pathol Pharmacol & Microbiol, Barcelona, Spain

来源：

PLOS ONE | 2011年 / 6卷 / 06期

关键词：

MANTLE CELL LYMPHOMA; DEFINED BURKITTS-LYMPHOMA; TRANSCRIPTION FACTOR; GENE-EXPRESSION; HIGH-RESOLUTION; DNA METHYLATION; NUCLEAR EXPRESSION; CANCER; MICROARRAY; SURVIVAL;

D O I：

10.1371/journal.pone.0021382

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

共 37 条

[1] APC/CCdc20 controls the ubiquitin-mediated degradation of p21 in prometaphase [J].