Long terminal repeats are used as alternative promoters for the endothelinB receptor and apolipoprotein C-I genes in humans

To examine the potential regulatory involvement of retroelements in the hum an genome, we screened the transcribed sequences of GenBank(TM) and express ed sequence tag data bases with long terminal repeat (LTR) elements derived from different human endogenous retroviruses. These screenings detected hu man transcripts containing LTRs belonging to the human endogenous retroviru s-E family fused to the apolipoprotein CI (apoC-I) and the endothelin B rec eptor (EBR) genes. However, both genes are known to have non-LTR (native) p romoters. Initial reverse transcription-polymerase chain reaction experimen ts confirmed and authenticated the presence of transcripts from both the na tive and LTR promoters. Using a 5'-rapid amplification of cDNA ends protoco l, we showed that the alternative transcripts of apoC-I and EBR are initiat ed and promoted by the LTRs, The LTR-apoC-I fusion and native apoC-I transc ripts are present in many of the tissues tested. As expected, we found apoC -I preferentially expressed in liver, where about 15% of the transcripts ar e derived from the LTR promoter, Transient transfections suggest that the e xpression is not dependent on the LTR itself, but the presence of the LTR i ncreases activity of the apoC-I promoter from both humans and baboons, The native EBR-driven transcripts were also detected in many tissues, whereas t he LTR-driven transcripts appear limited to placenta. In contrast to the LT R of apoC-I, the EBR LTR promotes a significant proportion of the total EBR transcripts, and transient transfection results indicate that the LTR acts as a strong promoter and enhancer in a placental cell line. This investiga tion reports two examples where LTR sequences contribute to increased trans cription of human genes and illustrates the impact of mobile elements on ge ne and genome evolution.