Use of the B cell transcription program results in hypomethylation and overexpression of key genes in EBV-mediated conversion of resting to proliferative B cells
Ontology highlight
ABSTRACT: We investigated the effects of experimental EBV infection of B cells on DNA methylation profiles by using high-throughput analysis. Remarkably, we observed hypomethylation of around 250 genes, but no hypermethylation. Hypomethylation did not occur at repetitive sequences, consistent with the absence of genomic instability in lymphoproliferative cells. Changes in methylation only occurred after cell divisions started, without the participation of the active demethylation machinery, and were concomitant with acquisition of B cells of the ability to proliferate. Gene ontology analysis, expression profiling, high-throughput analysis of the presence of transcription factor-binding motifs and occupancy revealed that most genes undergoing hypomethylation are active and display the presence of NFkB p65 and other B cell-specific transcription factors. Promoter hypomethylation associated with upregulation of genes relevant for the phenotype of proliferating lymphoblasts. Interestingly, pharmacologically-induced demethylation increased the efficiency of transformation of resting B cells to lymphoblastoid cells, suggesting the establishment of a productive cooperation between hypomethylation and lymphocyte proliferation. Bisulfite-converted DNA from 12 samples (6 Bcell, 6 Bcell immortalized) were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2.
ORGANISM(S): Homo sapiens
SUBMITTER: Fatima Al-Shahrour
PROVIDER: E-GEOD-41957 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
ACCESS DATA