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Background One member of the W family of human endogenous retroviruses (HERV) appears to have been functionally adopted by the human host. Nevertheless, a highly diversified and regulated transcription from a range of HERV-W elements has been observed in human tissues and cells. Aberrant expression of members of this family has also been associated with human disease such as multiple sclerosis (MS) and schizophrenia. It is not known whether this broad expression of HERV-W elements represents transcriptional leakage or specific transcription initiated from the retroviral promoter in the long terminal repeat (LTR) region. Therefore, potential influences of genomic context, structure and orientation on the expression levels of individual HERV-W elements in normal human tissues were systematically investigated. Results Whereas intronic HERV-W elements with a pseudogene structure exhibited a strong anti-sense orientation bias, intronic elements with a proviral structure and solo LTRs did not. Although a highly variable expression across tissues and elements was observed, systematic effects of context, structure and orientation were also observed. Elements located in intronic regions appeared to be expressed at higher levels than elements located in intergenic regions. Intronic elements with proviral structures were expressed at higher levels than those elements bearing hallmarks of processed pseudogenes or solo LTRs. Relative to their corresponding genes, intronic elements integrated on the sense strand appeared to be transcribed at higher levels than those integrated on the anti-sense strand. Moreover, the expression of proviral elements appeared to be independent from that of their corresponding genes. Conclusions Intronic HERV-W provirus integrations on the sense strand appear to have elicited a weaker negative selection than pseudogene integrations of transcripts from such elements. Our current findings suggest that the previously observed diversified and tissue-specific expression of elements in the HERV-W family is the result of both directed transcription (involving both the LTR and internal sequence) and leaky transcription of HERV-W elements in normal human tissues.

Background Human endogenous retroviruses (HERV) constitute approximately 8% of the human genome and have long been considered "junk". The sheer number and repetitive nature of these elements make studies of their expression methodologically challenging. Hence, little is known of transcription of genomic regions harboring such elements. Results Applying a recently developed technique for obtaining high resolution melting temperature data, we examined the frequency distributions of HERV-W gag element into 13 Tm categories in human tissues. Transcripts containing HERV-W gag sequences were expressed in non-random patterns with extensive variations in the expression between both tissues, including different brain regions, and individuals. Furthermore, the patterns of such transcripts varied more between individuals in brain regions than other tissues. Conclusion Thus, regulated expression of non-coding regions of the human genome appears to include the HERV-W family of repetitive elements. Although it remains to be established whether such expression patterns represent leakage from transcription of functional regions or specific transcription, the current approach proves itself useful for studying detailed expression patterns of repetitive regions.