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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1980-9-23
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pubmed:abstractText |
The nucleoside analog 5-azacytidine (5-aza-CR) induced marked changes in the differentiated state of cultured mouse embryo cells and also inhibited the methylation of newly synthesized DNA. The DNA strand containing 5-aza-CR remained undermethylated in the round of DNA synthesis following analog incorporation. The extent of inhibition of DNA modification and induction of muscle cells in treated cultures were dependent on the 5-aza-CR concentration over a narrow dose range. Experiments with the restriction enzyme Hpa II, which is sensitive to cytosine methylation in the sequence CCGG, demonstrated that the DNA synthesized in 5-aza-CR-treated cultures was maximally undermethylated 48 hr after treatment. Three other analogs of cytidine, containing a modification in the 5 position of the pyrimidine ring [5-aza-2'-deoxycytidine(5-aza-CdR), pseudoisocytidine (psi ICR) and 5-fluoro-2'-deoxycytidine(FCdR)] also induced the formation of muscle cells and inhibited DNA methylation. In contrast, 1-beta-D-arabinofuranosylcytosine (araC) and 6-azacytidine (6-aza-CR) did not inhibit DNA methylation or induce muscle formation, whereas 5-6-dihydro-5-azacytidine (dH-aza-CR) was a poor inducer of muscle cells and a poor inhibitor of DNA methylation. These results provide experimental evidence for a role for DNA modification in differentiation, and suggest that cytidine analogs containing an altered 5 position perturb previously established methylation patterns to yield new cellular phenotypes.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Azacitidine,
http://linkedlifedata.com/resource/pubmed/chemical/Cytarabine,
http://linkedlifedata.com/resource/pubmed/chemical/Cytidine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA (Cytosine-5-)-Methyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxycytidine,
http://linkedlifedata.com/resource/pubmed/chemical/Methyltransferases
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0092-8674
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
85-93
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:6156004-Adipose Tissue,
pubmed-meshheading:6156004-Animals,
pubmed-meshheading:6156004-Azacitidine,
pubmed-meshheading:6156004-Cell Differentiation,
pubmed-meshheading:6156004-Cells, Cultured,
pubmed-meshheading:6156004-Cytarabine,
pubmed-meshheading:6156004-Cytidine,
pubmed-meshheading:6156004-DNA,
pubmed-meshheading:6156004-DNA (Cytosine-5-)-Methyltransferase,
pubmed-meshheading:6156004-Deoxycytidine,
pubmed-meshheading:6156004-Methylation,
pubmed-meshheading:6156004-Methyltransferases,
pubmed-meshheading:6156004-Mice,
pubmed-meshheading:6156004-Muscles,
pubmed-meshheading:6156004-Structure-Activity Relationship
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pubmed:year |
1980
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pubmed:articleTitle |
Cellular differentiation, cytidine analogs and DNA methylation.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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