title: Epigenetic activation of SOX11 in lymphoid neoplasms by histone modifications.
abstract: 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.
authors: Hematopathology Section, Laboratory of Pathology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors: Maria Carmela
authors: MC
authors: Vegliante
authors: Cristina
authors: C
authors: Royo
authors: Jara
authors: J
authors: Palomero
authors: Itziar
authors: I
authors: Salaverria
authors: Balazs
authors: B
authors: Balint
authors: Idoia
authors: I
authors: Martín-Guerrero
authors: Xabier
authors: X
authors: Agirre
authors: Amaia
authors: A
authors: Lujambio
authors: Julia
authors: J
authors: Richter
authors: Silvia
authors: S
authors: Xargay-Torrent
authors: Silvia
authors: S
authors: Bea
authors: Luis
authors: L
authors: Hernandez
authors: Anna
authors: A
authors: Enjuanes
authors: María José
authors: MJ
authors: Calasanz
authors: Andreas
authors: A
authors: Rosenwald
authors: German
authors: G
authors: Ott
authors: José
authors: J
authors: Roman-Gomez
authors: Felipe
authors: F
authors: Prosper
authors: Manel
authors: M
authors: Esteller
authors: Pedro
authors: P
authors: Jares
authors: Reiner
authors: R
authors: Siebert
authors: Elias
authors: E
authors: Campo
authors: José I
authors: JI
authors: Martín-Subero
authors: Virginia
authors: V
authors: Amador
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008223:Lymphoma / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055751:SOXC Transcription Factors / Q000235:genetics*
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; C097473:SOX11 protein, human; D055751:SOXC Transcription Factors