Source:http://linkedlifedata.com/resource/pubmed/id/20497257
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2011-3-17
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pubmed:abstractText |
DNA and histone methylation are epigenetic modifications functioning in transcriptional control and have been implicated in the deregulation of gene expression in cancer. As a first step to determine if histone methylation could be involved in testis cancer pathogenesis, we performed immunofluorescent localization of histone H3 methylation at lysine 4 (H3-K4; gene activating) and lysine 9 (H3-K9; gene silencing) in healthy testis tissue and in samples of non-seminoma germ-cell tumours. In healthy testis, the distribution of histone H3 methylation was dependent on the developmental stage of spermatogenic cells and in non-seminoma, histone H3-K4 and K9 methylation was detected in all histological subtypes. This suggested that histone H3-K4 and K9 methylation could be associated with abnormal gene expression in non-seminoma. To determine the gene-specific function of histone H3 methylation, we proceeded to define the epigenetic status of key genes implicated in the pathogenesis of non-seminoma, namely the proto-oncogene POU5F1, which is overexpressed in testis cancer, and the tumour suppressor RASSF1A, which is aberrantly silenced. Cell lines representative of non-seminoma were treated with the chromatin-modifying drug, 5-aza-2'-deoxycytidine (5-aza-dC). Chromatin immunoprecipitation and real-time polymerase chain reaction analyses revealed that treatment with 5-aza-dC restored RASSF1A expression through a loss of gene silencing H3-K9 methylation and by retention of gene activating H3-K4 tri-methylation in the promoter region. In contrast, the expression of POU5F1 was reduced by 5-aza-dC and was associated with a loss of gene activating H3-K4 di-methylation in the promoter region. Analysis of DNA methylation revealed a slight reduction in DNA hypermethylation at the RASSF1A promoter, whereas the POU5F1 promoter remained mostly unmethylated and unaffected. Our results indicate that the effects of 5-aza-dC on histone methylation profiles are gene-specific and that aberrant histone modifications may serve as a principal means of misregulation of RASSF1A and POU5F1 expression in testis cancer.
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pubmed:grant | |
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/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Lysine,
http://linkedlifedata.com/resource/pubmed/chemical/Octamer Transcription Factor-3,
http://linkedlifedata.com/resource/pubmed/chemical/POU5F1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/RASSF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/decitabine
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1365-2605
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
34
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
110-23
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pubmed:meshHeading |
pubmed-meshheading:20497257-Azacitidine,
pubmed-meshheading:20497257-Gene Silencing,
pubmed-meshheading:20497257-Histones,
pubmed-meshheading:20497257-Humans,
pubmed-meshheading:20497257-Lysine,
pubmed-meshheading:20497257-Male,
pubmed-meshheading:20497257-Methylation,
pubmed-meshheading:20497257-Octamer Transcription Factor-3,
pubmed-meshheading:20497257-Testicular Neoplasms,
pubmed-meshheading:20497257-Tumor Suppressor Proteins
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pubmed:year |
2011
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pubmed:articleTitle |
Histone methylation is a critical regulator of the abnormal expression of POU5F1 and RASSF1A in testis cancer cell lines.
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pubmed:affiliation |
Department of Animal Science, McGill University, Montreal, Quebec, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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