Long Terminal Repeats Are Used as Alternative Promoters for the Endothelin B Receptor and Apolipoprotein C-I Genes in Humans

• Published in: The Journal of biological chemistry Vol. 276; no. 3; pp. 1896 - 1903
• Main Authors: Medstrand, Patrik, Landry, Josette-Renée, Mager, Dixie L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.01.2001; American Society for Biochemistry and Molecular Biology
• Subjects: Alternative Splicing; Animals; ApoC-I gene; Apolipoprotein C-I; Apolipoprotein CI; Apolipoproteins C - genetics; Base Sequence; DNA; EBR gene; Endogenous Retroviruses - genetics; Humans; long terminal repeats; Molecular Sequence Data; Promoter Regions, Genetic; Receptor, Endothelin B; Receptors, Endothelin - genetics; Retrovirus; RNA, Messenger - genetics; Terminal Repeat Sequences
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M006557200

To examine the potential regulatory involvement of retroelements in the human genome, we screened the transcribed sequences of GenBankTM and expressed sequence tag data bases with long terminal repeat (LTR) elements derived from different human endogenous retroviruses. These screenings detected human transcripts containing LTRs belonging to the human endogenous retrovirus-E family fused to the apolipoprotein CI (apoC-I) and the endothelin B receptor (EBR) genes. However, both genes are known to have non-LTR (native) promoters. Initial reverse transcription-polymerase chain reaction experiments confirmed and authenticated the presence of transcripts from both the native and LTR promoters. Using a 5′-rapid amplification of cDNA ends protocol, we showed that the alternative transcripts of apoC-I and EBR are initiated and promoted by the LTRs. The LTR-apoC-I fusion and native apoC-I transcripts are present in many of the tissues tested. As expected, we found apoC-I preferentially expressed in liver, where about 15% of the transcripts are derived from the LTR promoter. Transient transfections suggest that the expression is not dependent on the LTR itself, but the presence of the LTR increases activity of the apoC-I promoter from both humans and baboons. The native EBR-driven transcripts were also detected in many tissues, whereas the LTR-driven transcripts appear limited to placenta. In contrast to the LTR 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 investigation reports two examples where LTR sequences contribute to increased transcription of human genes and illustrates the impact of mobile elements on gene and genome evolution.