Linked Life Data

21690294

Source:http://linkedlifedata.com/resource/pubmed/id/21690294

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2011-7-28
pubmed:abstractText
Transcriptional silencing selectively impedes gene expression. Silencing is often accompanied by replication delay and can be prevented by replicator sequences. Here we report a replicator-binding protein complex involved in the prevention of transcriptional silencing. The protein complex interacts with an essential asymmetric region within the human ?-globin Rep-P replicator and includes hnRNP C1/C2, SWI/SNF complex, and MeCP1, which are members of the locus control region (LCR)-associated remodeling complex (LARC). Interaction between LARC and Rep-P prevented transcriptional silencing and replication delay. Transgenes that did not contain the asymmetric LARC-binding region of Rep-P replicated late and exhibited stable silencing that could not be affected by a DNA methylation inhibitor. In contrast, transgenes that contain a mutation of the asymmetric region of Rep-P that could not bind LARC exhibited a silent state that could transiently be reactivated by DNA demethylation. The effect of DNA demethylation was transient, and prolonged exposure to a methylation inhibitor induced distinct, stable, methylation-independent silencing. These observations suggest that the interaction of LARC complex with replicators plays a role in preventing gene silencing and provides support for a novel, epigenetic mechanism of resistance to methylation inhibitors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1098-5549
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3472-84
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Prevention of transcriptional silencing by a replicator-binding complex consisting of SWI/SNF, MeCP1, and hnRNP C1/C2.
pubmed:affiliation
Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Intramural