Abstract
The pituitary hormone prolactin (PRL) is best known for its role in the regulation of lactation. Recent evidence furthermore indicates PRL is required for normal reproduction in rodents. Here, we report on the insertion of two transposon-like DNA sequences in the human prolactin gene, which together function as an alternative promoter directing extrapituitary PRL expression. Indeed, the transposable elements contain transcription factor binding sites that have been shown to mediate PRL transcription in human uterine decidualised endometrial cells and lymphocytes. We hypothesize that the transposon insertion event has resulted in divergent (pituitary versus extrapituitary) expression of prolactin in primates, and in differential actions of pituitary versus extrapituitary prolactin in lactation versus pregnancy respectively. Importantly, the TE insertion might provide a context for some of the conflicting results obtained in studies of PRL function in mice and man. BioEssays 28: 1051–1055, 2006. © 2006 Wiley Periodicals, Inc.
Highlights
The polypeptide hormone prolactin (PRL) is produced mainly by the lactotrope cells of the anterior pituitary and, in mammals, its most apparent function is the regulation of Abbreviations: PRL, prolactin; transposable elements (TEs), transposable element; kB, kilobase; mRNA, messenger RNA; untranslated regions (UTRs), untranslated region; LTR, long terminal repeat; medium frequency reiterated repeat (MER), medium reiterated frequency repeat; CRE, cAMP-responsive element; CAAT/enhancer binding protein (C/EBP), CAAT enhancer-binding protein.lactation.[1]
Humans and in the rhesus macaque.[7,8,19] Intriguingly, by screening the PRL gene using the UCSC Genome Browser and its RepeatMasker facility, we observed that the proximal part of the extrapituitary PRL promoter, as well as exon 1a and a part of intronic sequence (Chr6: 22,410,692–22,411,189 1⁄4 498 bp), occur within a long terminal repeat (LTR)-like transposable element (TE) of the medium frequency reiterated repeat (MER) family.[20]. The LTR sequence belongs to the ERV1 class of endogenous retroviruses and it is present in the Rhesus macaque and chimpanzee PRL gene, but not in dog, mouse or rat genomes (Fig. 1)
It is likely that the MER20 TE integrated before mammalian radiation, 70–80 million years ago, but is not found by Repeatmasker in mice due to the higher neutral mutation rate in rodents, making ancient TEs difficult to detect.[21]. Several reports have demonstrated that TE-derived sequences can regulate nearby human genes
Summary
The polypeptide hormone prolactin (PRL) is produced mainly by the lactotrope cells of the anterior pituitary and, in mammals, its most apparent function is the regulation of Abbreviations: PRL, prolactin; TE, transposable element; kB, kilobase; mRNA, messenger RNA; UTR, untranslated region; LTR, long terminal repeat; MER, medium reiterated frequency repeat; CRE, cAMP-responsive element; C/EBP, CAAT enhancer-binding protein.lactation.[1]. *Correspondence to: Sarah Gerlo, Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Department of Molecular Biology, Ghent University, KL Ledeganckstraat 35, 9000
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