Cell type-specific expression and promoter activity of human endogenous retroviral long terminal repeats

Evolution over millions of years has adapted several thousand copies of ret rovirus-like elements and over 10 times as many solitary long terminal repe ats (LTRs) to their present location in the human genome. Transcription of these human endogenous retroviruses (HERVs) has been detected in various ce lls and tissues, and in some cases their transcriptional control elements h ave been recruited by cellular genes. We used a retroviral pol-specific exp ression array to obtain a HERV transcription profile in a variety of human cells such as epidermal keratinocytes, liver cells, kidney cells, pancreati c cells, lymphocytes, and lung fibroblasts. This rapid screening test revea led a distinct HERV pol-expression pattern in each cell type tested so far. About 40 different U3/R regulatory sequences from the HERV-H and HERV-W fa milies were then amplified from actively transcribed 3'HERV LTRs of various cell lines and tissues. Their promoter activities were compared with LTR s equences of other known HERV families in 12 human cell lines using a transi ent luciferase reporter system. Expression of the isolated HERV LTRs varied significantly in these cell lines, in some cases showing strict cell type specificity These results suggest that endogenous retroviral LTRs may be a valuable source of transcriptional regulatory elements for the construction of targeted retroviral expression vectors. (C) 2001 Academic Press.