Endogenous retrovirus long terminal repeats as ready-to-use mobile promoters: the case of primate beta3GAL-T5.
Throughout the course of vertebrate evolution, germline retroviral infections have resulted in heritable provirus insertions into host DNA. These endogenous retroviruses (ERVs) contain long terminal repeat (LTR) promoters that can be adopted for use by nearby host genes. It is not known whether the transcription factor (TF) binding sites and tissue-specificities of modern LTR gene promoters have been retained since the time of ERV insertion, or if these features evolved later as the LTR became involved in host gene regulation. To address this issue, we have conducted a case study of the ERV-L LTR promoter of human beta1,3-galactosyltransferase 5 (beta3GAL-T5). We have previously shown that the human beta3GAL-T5 LTR promoter is responsible for the majority of gene transcripts in the colon. The murine beta3gal-t5 gene is also expressed primarily in the colon, despite the absence of an orthologous ERV-L LTR in the mouse genome. We therefore hypothesized that both the ERV-L LTR and the non-retroviral ancestral beta3GAL-T5 promoter were active in the colon at the time of ERV insertion. In support of this hypothesis, we have shown that the orthologous LTRs of four non-human primates are also active in a human colorectal cell line, and that the baboon LTR is active in primary baboon colon tissue. We also present evidence that the functional TF binding sites of the human beta3GAL-T5 LTR promoter were present in the original consensus sequence for this class of LTRs. Upon similar analysis of other ERV sequences, we have concluded that this evolutionary history is shared by certain other LTR gene promoters, and may be a general phenomenon.
Dunn
Catherine A
CA
Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
van de Lagemaat
Louie N
LN
Baillie
Gregory J
GJ
Mager
Dixie L
DL
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003106:Colon / Q000821:virology; D017931:DNA Primers; D020077:Endogenous Retroviruses / Q000235:genetics*; D005700:Galactosyltransferases / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010215:Papio / Q000821:virology; D011323:Primates; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D020079:Terminal Repeat Sequences; D013737:Testis / Q000201:enzymology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics
D017931:DNA Primers; D014157:Transcription Factors; D014764:Viral Proteins; C479886:B3GALT5 protein, human; D005700:Galactosyltransferases