CmC(A/T)GG DNA methylation in mature B cell lymphoma gene silencing.
DNA methylation has been linked to gene silencing in cancer. Primary effusion lymphoma (PEL) and myeloma are lymphoid malignancies that arise from terminally differentiated B cells. Interestingly, PEL do not express immunoglobulins or most B lineage-specific genes. The B cell-specific B29 (Igbeta/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 demethylating and histone deacetylase inhibiting treatments. Bisulfite sequencing revealed two types of DNA methylation in silenced B29 promoters: at conventional CpG and at CC(A/T)GG B29 promoter sites. The pattern of methylated CpG ((m)CpG) and C(m)C(A/T)GG B29 promoter methylation observed was similar to that recently reported for epigenetic silencing of an integrated retrovirus. Methylation of C(m)C(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 factor. This methylated motif formed DNA-protein complexes with nuclear extracts from all cell types examined. Therefore, C(m)C(A/T)GG methylation may represent an important type of epigenetic marker on mammalian DNA that impacts transcription by altering DNA-protein complex formation.
Malone
C S
CS
Department of Microbiology and Immunology, Jonsson Comprehensive Cancer Center, University of California, Center for the Health Sciences, Los Angeles, CA 90095, USA.
Miner
M D
MD
Doerr
J R
JR
Jackson
J P
JP
Jacobsen
S E
SE
Wall
R
R
Teitell
M
M
D015703:Antigens, CD / Q000235:genetics; D001483:Base Sequence; D051925:CD79 Antigens; D019175:DNA Methylation; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D020868:Gene Silencing; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000378:metabolism; D046911:Macromolecular Substances; D009363:Neoplasm Proteins / Q000737:chemistry; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000378:metabolism
D015703:Antigens, CD; D051925:CD79 Antigens; D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D015534:Trans-Activators