Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-3-6
pubmed:abstractText
Many B-lineage-specific genes are down-regulated in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). We investigated the involvement of epigenetic modifications in gene silencing in cHL cell lines and in microdissected primary HRS cells. We assessed the expression and methylation status of CD19, CD20, CD79B, SYK, PU.1, BOB.1/OBF.1, BCMA, and LCK, all of which are typically down-regulated in cHL. We could reactivate gene expression in cHL cell lines with the DNA demethylating agent 5-aza-deoxycytidine (5-aza-dC). Using methylation-specific polymerase chain reaction (MSP), bisulfite genomic sequencing, and digestion with methylation-sensitive endonuclease followed by polymerase chain reaction (PCR), we determined the methylation status of promoter regions of PU.1, BOB.1/OBF.1, CD19, SYK, and CD79B. Down-regulation of transcription typically correlated with hypermethylation. Using bisulfite genomic sequencing we found that in microdissected HRS cells of primary cHL SYK, BOB.1/OBF.1, and CD79B promoters were also hypermethylated. Ectopic expression of both Oct2 and PU.1 in a cHL cell line potentiated endogenous PU.1 and SYK expression after 5-aza-dC treatment. These observations indicate that silencing of the B-cell-specific genes in cHL may be the consequence of a compromised regulatory network where down-regulation of a few master transcription factors results in silencing of numerous genes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
107
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2493-500
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma.
pubmed:affiliation
Department of Physiological Chemistry, University of Ulm, D-89069 Ulm, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't