SOXC transcription factors in mantle cell lymphoma: the role of promoter methylation in SOX11 expression

Abstract

The related transcription factors SOX11, SOX4 and SOX12 (classified as the SOXC family) compete for the same target genes. SOX11 is expressed in most mantle cell lymphomas (MCL) but a small subset is, like normal lymphocytes, SOX11 negative. Here we report the variable expression of SOX4 and high expression of SOX12 in MCL compared to non-malignant tissue. Our results show that the expression of the SOXC genes is highly correlated in SOX11 positive MCL. SOX11 expression is epigenetically regulated but there are partly conflicting results regarding the underlying mechanisms. Here we report that the SOX11 promoter region is hypomethylated in both MCL and normal B-lymphocytes. Methylation at other sites is important for sustaining high SOX11 in MCL since treatment with 5-azacytidine decreased SOX11 levels in SOX11 positive MCL cell lines: Granta519 and Rec1. Furthermore, 5-azacytidine treatment of the SOX11 negative MCL cell line, JVM2, induced SOX4 but not SOX11.