Linked Life Data

19221495

Source:http://linkedlifedata.com/resource/pubmed/id/19221495

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-3-16
pubmed:abstractText
Differentiation and malignant transformation of stem cells are regulated by epigenetic mechanisms. We analyzed promoter methylation and expression of the stem cell determining genes Brachyury, DPPA5, FGF4, FOXD3, LIN28, NESTIN and ZFP42 depending on the differentiation state in human mesenchymal stem cells (MSC), human embryonal carcinoma cells (ECC) and somatic tumor cells. Differentiation of MSC into osteoblasts and adipocytes was accompanied with a loss of expression of the Brachyury gene and downregulation of LIN28. Inactivation of Brachyury was associated with progressive methylation of its CpG island promoter. In ECC promoter methylation of stem cell markers was more frequent in the differentiated subgroup (71%) compared to undifferentiated ECC (29%) and this was associated with downregulation of Brachyury, DPPA5, FGF4, FOXD3, LIN28 and ZFP42. DPPA5 was methylated and NESTIN was unmethylated in most tumor cells. In somatic tumor cells, methylation of stem cell markers (Brachyury, DPPA5, FGF4, FOXD3, LIN28 and ZFP42) was frequently observed (85%). Treatment of cell lines with an inhibitor of DNA methyltransferase reactivated the expression of DPPA5, FGF4, FOXD3, LIN28 and ZFP42, indicating that aberrant promoter methylation is a crucial event that results in their silencing. Our results suggest that epigenetic inactivation of stem cell associated genes is mediated by promoter methylation and that this may represent a fundamental mechanism during normal differentiation processes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1551-4005
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
916-24
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
The role of promoter CpG methylation in the epigenetic control of stem cell related genes during differentiation.
pubmed:affiliation
Institute for Genetics, Justus-Liebig University Giessen, Giessen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't