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Background  The neural transcription factor SOX11 is present at specific stages during embryo development with a very restricted expression in adult tissue, indicating precise regulation of transcription. SOX11 is strongly up-regulated in some malignancies and have a functional role in tumorgenesis. With the aim to explore differences in epigenetic regulation of SOX11 expression in normal versus neoplastic cells, we investigated methylation and histone modifications related to the SOX11 promoter and the possibility to induce re-expression using histone deacetylase (HDAC) or EZH2 inhibitors.    Methods  The epigenetic regulation of  SOX11  was investigated in distinct non-malignant cell populations (n = 7) and neoplastic cell-lines (n = 42) of different cellular origins. DNA methylation was assessed using bisulfite sequencing, methylation-specific melting curve analysis, MethyLight and pyrosequencing. The presence of H3K27me3 was assessed using ChIP-qPCR. The HDAC inhibitors Vorinostat and trichostatin A were used to induce SOX11 in cell lines with no endogenous expression.    Results  The  SOX11  promoter shows a low degree of methylation and strong enrichment of H3K27me3 in non-malignant differentiated cells, independent of cellular origin. Cancers of the B-cell lineage are strongly marked by  de novo  methylation at the  SOX11  promoter in SOX11 non-expressing cells, while solid cancer entities display a more varying degree of  SOX11  promoter methylation. The silencing mark H3K27me3 was generally present at the  SOX11  promoter in non-expressing cells, and an increased enrichment was observed in cancer cells with a low degree of  SOX11  methylation compared to cells with dense methylation. Finally, we demonstrate that the HDAC inhibitors (vorinostat and trichostatin A) induce SOX11 expression in cancer cells with low levels of  SOX11  methylation.    Conclusions  We show that  SOX11  is strongly marked by repressive histone marks in non-malignant cells. In contrast, SOX11 regulation in neoplastic tissues is more complex involving both DNA methylation and histone modifications. The possibility to re-express SOX11 in non-methylated tissue is of clinical relevance, and was successfully achieved in cell lines with low levels of  SOX11  methylation. In breast cancer patients, methylation of the  SOX11  promoter was shown to correlate with estrogen receptor status, suggesting that SOX11 may be functionally re-expressed during treatment with HDAC inhibitors in specific patient subgroups.    Electronic supplementary material  The online version of this article (doi:10.1186/s12885-015-1208-y) contains supplementary material, which is available to authorized users.

DNA methylation and histone modifications regulate SOX11 expression in lymphoid and solid cancer cells