Linked Life Data

17828306

Source:http://linkedlifedata.com/resource/pubmed/id/17828306

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2008-2-28
pubmed:abstractText
Dysregulation of DNA methyltransferase (DNMT)1 expression is associated with cellular transformation, and inhibition of DNMT1 exerts antitumorigenic effects. Here, we report that DNMT1 abnormally expressed in HeLa cells is downregulated by a histone deacetylase (HDAC) inhibitor apicidin, which is correlated with induction of repressive histone modifications on the promoter site. Apicidin selectively represses the expression of DNMT1 among DNMTs in HeLa cells, independent of cell cycle arrest at G0/G1. Furthermore, apicidin causes a significant reduction in the recruitment of RNA polymerase II into the promoter. Chromatin immunoprecipitation analysis shows that even though apicidin causes global hyperacetylation of histone H3 and H4, localized deacetylation of histone H3 and H4 occurs at the E2F binding site, which is accompanied by the recruitment of pRB and the replacement of P/CAF with HDAC1 into the sites. In addition, K4-trimethylated H3 on nucleosomes associated with the transcriptional start site is depleted following apicidin treatment, whereas repressive markers, K9- and K27-trimethylation of H3 are enriched on the site. The downregulation of DNMT1 expression seems to require de novo protein synthesis, because the apicidin effect is antagonized by cycloheximide treatment. Moreover, knock down of DNMT1 with siRNA induces the apoptosis of HeLa cells, indicating that downregulation of DNMT1 might be a good strategy for therapeutics of human cervix cancer. Collectively, our findings will provide a mechanistic rationale for the use of HDAC inhibitors in cancer therapeutics.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1376-86
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17828306-Cell Line, Tumor, pubmed-meshheading:17828306-DNA (Cytosine-5-)-Methyltransferase, pubmed-meshheading:17828306-Down-Regulation, pubmed-meshheading:17828306-E2F Transcription Factors, pubmed-meshheading:17828306-Enzyme Inhibitors, pubmed-meshheading:17828306-Female, pubmed-meshheading:17828306-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17828306-HeLa Cells, pubmed-meshheading:17828306-Histone Deacetylase Inhibitors, pubmed-meshheading:17828306-Histones, pubmed-meshheading:17828306-Humans, pubmed-meshheading:17828306-Peptides, Cyclic, pubmed-meshheading:17828306-Promoter Regions, Genetic, pubmed-meshheading:17828306-Protein Transport, pubmed-meshheading:17828306-Repressor Proteins, pubmed-meshheading:17828306-Retinoblastoma Protein, pubmed-meshheading:17828306-Uterine Cervical Neoplasms
pubmed:year
2008
pubmed:articleTitle
Histone deacetylase inhibitor apicidin downregulates DNA methyltransferase 1 expression and induces repressive histone modifications via recruitment of corepressor complex to promoter region in human cervix cancer cells.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, College of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't