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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Retrovirology
2017 ; 14
(1
): 20
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DNA hypomethylation and aberrant expression of the human endogenous retrovirus
ERVWE1/syncytin-1 in seminomas
#MMPMID28302141
Bene?ová M
; Trejbalová K
; Ková?ová D
; Vernerová Z
; Hron T
; Ku?erová D
; Hejnar J
Retrovirology
2017[Mar]; 14
(1
): 20
PMID28302141
show ga
BACKGROUND: Syncytin-1 and 2, human fusogenic glycoproteins encoded by the env
genes of the endogenous retroviral loci ERVWE1 and ERVFRDE1, respectively,
contribute to the differentiation of multinucleated syncytiotrophoblast in
chorionic villi. In non-trophoblastic cells, however, the expression of syncytins
has to be suppressed to avoid potential pathogenic effects. Previously, we have
shown that the transcriptional suppression of ERVWE1 promoter is controlled
epigenetically by DNA methylation and chromatin modifications. In this study, we
describe the aberrant expression of syncytin-1 in biopsies of testicular germ
cell tumors. RESULTS: We found efficient expression and splicing of syncytin-1 in
seminomas and mixed germ cell tumors with seminoma component. Although another
fusogenic gene, syncytin-2 was also derepressed in seminomas, its expression was
significantly lower than that of syncytin-1. Neither the transcription factor
GCM1 nor the increased copy number of ERVWE1 were sufficient for this aberrant
expression of syncytin-1 in seminomas. In accordance with our recent finding of
the highly increased expression of TET1 dioxygenase in most seminomas, the ERVWE1
promoter was significantly hypomethylated in comparison with the matched
controls. In contrast, 5-hydroxymethylcytosine levels were not detectable at the
ERVWE1 promoter. We further describe that another endogenous retroviral element
adjacent to ERVWE1 remains transcriptionally suppressed and two additional HERV-W
family members are only slightly upregulated in seminomas. CONCLUSIONS: We
conclude that DNA demethylation of the ERVWE1 promoter in seminomas is a
prerequisite for syncytin-1 derepression. We propose the spliced syncytin-1
expression as a marker of seminoma and suggest that aberrant expression of
endogenous retroviruses might be a correlate of the hypomethylated genome of
seminomas.