C(m)C(A/T)GG DNA methylation in mature B cell lymphoma gene silencing

DNA methylation has been linked to gene silencing in cancer. Primary effusi on lymphoma (PEL) and myeloma are lymphoid malignancies that arise from ter minally differentiated B cells. Interestingly, PEL do not express immunoglo bulins or most B lineage-specific genes. The B cell-specific B29 (Ig beta / CD79b) gene is silenced in PEL and some myelomas but is expressed in other normal and malignant B cells. B29 expression was reactivated in PEL by deme thylating and histone deacetylase inhibiting treatments. Bisulfite sequenci ng revealed two types of DNA methylation in silenced B29 promoters: at conv entional CpG and at CC(A/T)GG B29 promoter sites. The pattern of methylated CpG ((m)CpG) and (CC)-C-m(A/T)GG B29 promoter methylation observed was sim ilar to that recently reported for epigenetic silencing of an integrated re trovirus. Methylation of CmC(A/T)GG sites in the B29 promoter significantly repressed in vivo transcriptional activity. Also, methylation of a central conserved C(m)CTGG B29 promoter site blocked the binding of early B cell f actor. This methylated motif formed DNA-protein complexes with nuclear extr acts from all cell types examined. Therefore, CmC(A/T)GG methylation may re present an important type of epigenetic marker on mammalian DNA that impact s transcription by altering DNA-protein complex formation.