Document Detail


NANOG promoter methylation and expression correlation during normal and malignant human germ cell development.
MedLine Citation:
PMID:  20930529     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Testicular germ cell tumors are the most frequent malignant tumors in young Caucasian males, with increasing incidence. The actual model of tumorigenesis is based on the theory that a block in maturation of fetal germ cells lead to formation of the intratubular germ cell neoplasia unclassified. Early fetal germ cells and undifferentiated germ cell tumors express pluripotency markers such as the transcription factor NANOG. It has been demonstrated, that epigenetic modifications such as promoter DNA-methylation is able to silence gene expression in normal and cancer cells. Here we show, that OCT3/4-SOX2 mediated expression of NANOG can be silenced by methylation of promoter CpG-sites. We found that global methylation of DNA decreased from fetal spermatogonia to mature sperm. In contrast, CpGs in the NANOG promoter were found hypomethylated in spermatogonia and hypermethylated in sperm. This selective repression might reflect the cells need to suppress pluripotency in order to prevent malignant transformation. Finally, methylation of CpGs in the NANOG promoter in germ cell tumors and derived cell lines correlated to differentiation state.
Authors:
Daniel Nettersheim; Katharina Biermann; Ad J M Gillis; Klaus Steger; Leendert H J Looijenga; Hubert Schorle
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-01-01
Journal Detail:
Title:  Epigenetics : official journal of the DNA Methylation Society     Volume:  6     ISSN:  1559-2308     ISO Abbreviation:  Epigenetics     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-26     Completed Date:  2011-04-25     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101265293     Medline TA:  Epigenetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  114-22     Citation Subset:  IM    
Affiliation:
Department of Developmental Pathology, Institute of Pathology, University of Bonn, Bonn, Germany.
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MeSH Terms
Descriptor/Qualifier:
Cell Differentiation / physiology*
Cell Line, Tumor
CpG Islands / physiology
DNA Methylation*
Gene Silencing*
Homeodomain Proteins / genetics,  metabolism*
Humans
Male
Neoplasms, Germ Cell and Embryonal / genetics,  metabolism*
Promoter Regions, Genetic*
Spermatogonia / metabolism*
Spermatozoa / metabolism*
Chemical
Reg. No./Substance:
0/Homeodomain Proteins; 0/NANOG protein, human
Comments/Corrections

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