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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2001-5-25
pubmed:abstractText
The molecular mechanisms underlying the activation of tissue-specific genes have not yet been fully clarified. We analyzed the methylation status of specific CCGG sites in the 5'-flanking region and exon 1 of myogenin gene, a very important myogenic differentiation factor. We demonstrated a loss of methylation, at the onset of C2C12 muscle cell line differentiation, limited to the CCGG site of myogenin 5'-flanking region, which was strongly correlated with the transcriptional activation of this gene and with myogenic differentiation. The same CCGG site was also found to be hypomethylated, in vivo, in embryonic mouse muscle (a myogenin-expressing tissue), as opposed to nonmuscle (nonexpressing) tissues that had a fully methylated site. In a C2C12-derived clone with enhanced myogenic ability, demethylation occurred within 2 h of induction of differentiation, suggesting the involvement of some active demethylation mechanism(s) that occur in the absence of DNA replication. Exposure to drugs that inhibit DNA methylation by acting on the S-adenosylmethionine metabolism produced a further reduction, to a few minutes, in the duration of the demethylation dynamics. These effects suggest that the final site-specific DNA methylation pattern of tissue-specific genes is defined through a continuous, relatively fast interplay between active DNA demethylation and re-methylation mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7500-6
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11096088-Animals, pubmed-meshheading:11096088-Brain, pubmed-meshheading:11096088-Cell Differentiation, pubmed-meshheading:11096088-Cell Line, pubmed-meshheading:11096088-CpG Islands, pubmed-meshheading:11096088-DNA, Complementary, pubmed-meshheading:11096088-DNA Methylation, pubmed-meshheading:11096088-DNA Replication, pubmed-meshheading:11096088-Homocystine, pubmed-meshheading:11096088-Mice, pubmed-meshheading:11096088-Models, Genetic, pubmed-meshheading:11096088-Muscle, Skeletal, pubmed-meshheading:11096088-Muscles, pubmed-meshheading:11096088-Myogenin, pubmed-meshheading:11096088-RNA, pubmed-meshheading:11096088-Rats, pubmed-meshheading:11096088-S-Adenosylmethionine, pubmed-meshheading:11096088-Spleen, pubmed-meshheading:11096088-Time Factors, pubmed-meshheading:11096088-Transcriptional Activation
pubmed:year
2001
pubmed:articleTitle
The dynamics of myogenin site-specific demethylation is strongly correlated with its expression and with muscle differentiation.
pubmed:affiliation
Department of Cellular Biotechnologies and Hematology and I Department of Surgery, University of Rome "La Sapienza," Rome, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't