title: Placenta-specific expression of the interleukin-2 (IL-2) receptor β subunit from an endogenous retroviral promoter.
abstract: The long terminal repeat (LTR) sequences of endogenous retroviruses and retroelements contain promoter elements and are known to form chimeric transcripts with nearby cellular genes. Here we show that an LTR of the THE1D retroelement family has been domesticated as an alternative promoter of human IL2RB, the gene encoding the β subunit of the IL-2 receptor. The LTR promoter confers expression specifically in the placental trophoblast as opposed to its native transcription in the hematopoietic system. Rather than sequence-specific determinants, DNA methylation was found to regulate transcription initiation and splicing efficiency in a tissue-specific manner. Furthermore, we detected the cytoplasmic signaling domain of the IL-2Rβ protein in the placenta, suggesting that IL-2Rβ undergoes preferential proteolytic cleavage in this tissue. These findings implicate novel functions for this cytokine receptor subunit in the villous trophoblast and reveal an intriguing example of ancient LTR exaptation to drive tissue-specific gene expression.
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3.
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Cohen
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3.
authors.forename: Rita
authors.initials: R
authors.lastname: Rebollo
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3.
authors.forename: Sonja
authors.initials: S
authors.lastname: Babovic
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Dai
authors.affiliation: Department of Medical Genetics, University of British Columbia, British Columbia V6T 1Z4; Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada.
authors.forename: Wendy P
authors.initials: WP
authors.lastname: Robinson
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3; Department of Medical Genetics, University of British Columbia, British Columbia V6T 1Z4. Electronic address: dmager@bccrc.ca.
authors.forename: Dixie L
authors.initials: DL
authors.lastname: Mager
mesh_terms: D019175:DNA Methylation / Q000502:physiology; D020077:Endogenous Retroviruses / Q000378:metabolism*; D005260:Female; D006801:Humans; D053646:Interleukin-2 Receptor beta Subunit / Q000096:biosynthesis*; D009928:Organ Specificity / Q000502:physiology; D011257:Pregnancy Proteins / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D020079:Terminal Repeat Sequences / Q000502:physiology*; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: C508020:IL2RB protein, human; D053646:Interleukin-2 Receptor beta Subunit; D011257:Pregnancy Proteins