Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-4-6
pubmed:abstractText
The expression of DNMT1, the major maintenance DNA methyltransferases, is critical in coordinating DNMT1 activity with biological processes and therefore must be tightly regulated in the cell cycle. Here, we report p21(WAF1) as a novel upstream regulator of DNMT1 expression. Ectopic expression of p21(WAF1) or TSA-mediated p21(WAF1) induction inhibits DNMT1 at the transcriptional level, and this observation consistently coincides with a reduction in p300. Furthermore, siRNA-mediated p300 knockdown significantly abolishes DNMT1 mRNA levels, demonstrating the dependence of DNMT1 expression on p300. Consistent with this, p300 enhances transactivation of DNMT1 promoter 340bp upstream of the initiation start site harboring the E2F1 and Sp1/3 binding sites. Collectively, we identified p300 as a crucial transcription regulator for DNMT1. We proposed that the reduction in p300 following p21(WAF1) up-regulation contributes to DNMT1 down-regulation. This novel p21(WAF1)-p300-DNMT1 pathway may play a pivotal role to ensure regulated DNMT1 expression and DNA methylation in mammalian cell division.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1090-2104
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
382
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
171-6
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
p21(WAF1) negatively regulates DNMT1 expression in mammalian cells.
pubmed:affiliation
Cell Death and Human Disease Group, Division of Cancer and Developmental Cell Biology, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Singapore 138673, Singapore. tanhh@imcb.a-star.edu.sg
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't