title: Expression patterns of transcribed human endogenous retrovirus HERV-K(HML-2) loci in human tissues and the need for a HERV Transcriptome Project.
abstract: BACKGROUND
  A significant proportion of the human genome is comprised of human endogenous retroviruses (HERVs). HERV transcripts are found in every human tissue. Expression of proviruses of the HERV-K(HML-2) family has been associated with development of human tumors, in particular germ cell tumors (GCT). Very little is known about transcriptional activity of individual HML-2 loci in human tissues, though.
  
  
  RESULTS
  By employing private nucleotide differences between loci, we assigned approximately 1500 HML-2 cDNAs to individual HML-2 loci, identifying, in total, 23 transcriptionally active HML-2 proviruses. Several loci are active in various human tissue types. Transcription levels of some HML-2 loci appear higher than those of other loci. Several HML-2 Rec-encoding loci are expressed in GCT and non-GCT tissues. A provirus on chromosome 22q11.21 appears strongly upregulated in pathologic GCT tissues and may explain high HML-2 Gag protein levels in GCTs. Presence of Gag and Env antibodies in GCT patients is not correlated with activation of individual loci. HML-2 proviruses previously reported capable of forming an infectious HML-2 variant are transcriptionally active in germ cell tissue. Our study furthermore shows that Expressed Sequence Tag (EST) data are insufficient to describe transcriptional activity of HML-2 and other HERV loci in tissues of interest.
  
  
  CONCLUSIONS
  Our, to date, largest-scale study reveals in greater detail expression patterns of individual HML-2 loci in human tissues of clinical interest. Moreover, large-scale, specialized studies are indicated to better comprehend transcriptional activity and regulation of HERVs. We thus emphasize the need for a specialized HERV Transcriptome Project.
authors.affiliation: Department of Human Genetics, Medical Faculty, University of Saarland, Homburg, Germany. aline.flockerzi@uniklinik-saarland.de
authors.forename: Aline
authors.initials: A
authors.lastname: Flockerzi
authors.forename: Alessia
authors.initials: A
authors.lastname: Ruggieri
authors.forename: Oliver
authors.initials: O
authors.lastname: Frank
authors.forename: Marlies
authors.initials: M
authors.lastname: Sauter
authors.forename: Esther
authors.initials: E
authors.lastname: Maldener
authors.forename: Bernd
authors.initials: B
authors.lastname: Kopper
authors.forename: Bernd
authors.initials: B
authors.lastname: Wullich
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Seifarth
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Müller-Lantzsch
authors.forename: Christine
authors.initials: C
authors.lastname: Leib-Mösch
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
authors.forename: Jens
authors.initials: J
authors.lastname: Mayer
mesh_terms: D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D001940:Breast / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000235:genetics; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000378:metabolism; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics; D011533:Proviruses / Q000235:genetics* / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; C485839:ERVK-6 protein, human endogenous retrovirus; D014759:Viral Envelope Proteins