Functional mapping of the bovine Doppel gene promoter region

Vecchio, Igor Del; Azzalin, Alberto; Guidi, Elena; Amati, Giuseppe; Caramori, Tiziana; Uboldi, Cristina; Comincini, Sergio; Ferretti, Luca

doi:10.1016/j.gene.2005.04.028

Cited by 6 publications

(6 citation statements)

References 14 publications

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“…The basic structure of the prion-promoter region consisted of four conserved short nucleotide motifs. However, as reported in different contributions [45][46][47][48], the doppel promoter did not show any of the prion promoter motifs, lacking also the typical eukaryotic TATA and CpG islands. These characteristics, together with the possible binding of regulatory molecules (Brn-3a and Brn-3b), the presence of cis-acting elements (CCAAT and E boxes) as well as the interaction with inhibitory elements, might reflect a complex and modulated transcription capability to the doppel promoter.…”

Section: Looking For Doppel Functionssupporting

confidence: 55%

The doppel gene biology: a scientific journey from brain to testis, and return

2006

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Doppel is a newly recognized prion-like molecule encoded by a novel gene locus, PRND, located on the same chromosomal region of the prion (PRNP) coding gene. Doppel was considered a paralogue and the first member of the prion-gene family, possibly originated through an ancestral gene duplication event. Prion and doppel have different expression patterns, suggesting that the gene products exhibit different biological functions. Actually, doppel is not involved in the aetiology of the Transmissible Spongiform Encephalopathies (TSEs) or "prion diseases" and is highly expressed only within the testicular tissue, suggesting an important physiological role in the process of spermatogenesis. The restricted spatial and temporal expression profile of doppel has suggested its investigation within particular pathological contexts, such as cancers, showing that it might represent a novel and attractive diagnostic molecular marker and that might provide insights into the regulatory pathways of tumor-cell transformation.

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Section: Looking For Doppel Functionssupporting

confidence: 55%

The doppel gene biology: a scientific journey from brain to testis, and return

2006

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“…The PRND core promoter region [24] is conserved between human and mammals, and it includes highly conserved CCAAT, CArG and TATA elements (Figure 2C). PRND has an unclear mode of expression that is developmentally regulated [7,10,24].…”

Section: Resultsmentioning

confidence: 99%

“…PRNP , PRND , PRNT and SPRN show similar gene organisations, which encompass two or three exons [7,10,13,22]. However, while the eutherian PRNP and SPRN promoters incorporate CpG islands, the tissue-specific PRND and PRNT promoters do not include CpG islands [10,11,22,24]. Furthermore, PRNP and SPRN are present in both eutherians and fish (the two PRNP homologues in fish are PrP1 and PrP2 ) but PRND was found only in eutherians, and PRNT was found only in primates [11,12,25].…”

Section: Introductionmentioning

confidence: 99%

Comparative genomic analysis of prion genes

2007

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Background: The homologues of human disease genes are expected to contribute to better understanding of physiological and pathogenic processes. We made use of the present availability of vertebrate genomic sequences, and we have conducted the most comprehensive comparative genomic analysis of the prion protein gene PRNP and its homologues, shadow of prion protein gene SPRN and doppel gene PRND, and prion testis-specific gene PRNT so far. Results:While the SPRN and PRNP homologues are present in all vertebrates, PRND is known in tetrapods, and PRNT is present in primates. PRNT could be viewed as a TEassociated gene. Using human as the base sequence for genomic sequence comparisons (VISTA), we annotated numerous potential cis-elements. The conserved regions in SPRNs harbour the potential Sp1 sites in promoters (mammals, birds), C-rich intron splicing enhancers and PTB intron splicing silencers in introns (mammals, birds), and hsamiR-34a sites in 3'-UTRs (eutherians). We showed the conserved PRNP upstream regions, which may be potential enhancers or silencers (primates, dog). In the PRNP 3'-UTRs, there are conserved cytoplasmic polyadenylation element sites (mammals, birds). The PRND core promoters include highly conserved CCAAT, CArG and TATA boxes (mammals). We deduced 42 new protein primary structures, and performed the first phylogenetic analysis of all vertebrate prion genes. Using the protein alignment which included 122 sequences, we constructed the neighbour-joining tree which showed four major clusters, including shadoos, shadoo2s and prion protein-likes (cluster 1), fish prion proteins (cluster 2), tetrapode prion proteins (cluster 3) and doppels (cluster 4). We showed that the entire prion protein conformationally plastic region is well conserved between eutherian prion proteins and shadoos (18-25% identity and 28-34% similarity), and there could be a potential structural compatibility between shadoos and the left-handed parallel beta-helical fold. Conclusion:It is likely that the conserved genomic elements identified in this analysis represent bona fide cis-elements. However, this idea needs to be confirmed by functional assays in transgenic systems.

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“…2B). As previously reported, ROX molecular weight standards migrate as if they were approximately 3 nt longer (Del Vecchio et al, 2005 and. This bias was analyzed and corrected by using the Big Dyes sequence.…”

Section: Floe Primer Extension Analysis Of the Human Gnb2l1 Mrnamentioning

confidence: 99%

“…FLOE was conducted as reported in (Del Vecchio et al, 2005 and. In brief, total RNA from human THP1 monocytic cells was isolated using Trizol ® Reagent (Invitrogen, Carlsbad, CA) and quantified using a DU ® 530 UV/Vis Spectrophotometer (Beckman Coulter Inc., Fullerton, CA).…”

Section: Floe Primer Extension Analysismentioning

confidence: 99%