The Pxmp2 and PoleI genes are linked by a bidirectional promoter in an evolutionary conserved fashion

Otte, David M.; Schwaab, U.; Lüers, Georg H.

doi:10.1016/s0378-1119(03)00667-x

Cited by 9 publications

(5 citation statements)

References 27 publications

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“…The translation initiation codons of these two genes are separated by only 393 bp. Pxmp2 and PoleI have been shown to have independently regulated expression [42]. To produce Pxmp2 deficiency, a targeting vector was constructed such that after homologous recombination of the disruption cassette at exon 2 of Pxmp2 , a 2.7 kb segment flanking the region 5′ of the translation initiation code in PoleI remained intact (Figure S1A).…”

Section: Methodsmentioning

confidence: 99%

“…The inactivation of Pxmp2 was further demonstrated by immunodetection of the corresponding protein in liver homogenates from wild-type, Pxmp2 +/− and Pxmp2 −/− mice (Figure 1A). The proximity of PoleI to Pxmp2 prompted us to investigate the expression of this gene in spleen, a tissue with a high rate of cell proliferation characterized by a substantial level of PoleI expression [42]. The results of quantitative real time PCR showed no difference in the expression levels between wild-type and Pxmp2-deficient mice, indicating that the expression of PoleI was not affected by the disruption of Pxmp2 .…”

Section: Methodsmentioning

confidence: 99%

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Pxmp2 Is a Channel-Forming Protein in Mammalian Peroxisomal Membrane

et al. 2009

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BackgroundPeroxisomal metabolic machinery requires a continuous flow of organic and inorganic solutes across peroxisomal membrane. Concerning small solutes, the molecular nature of their traffic has remained an enigma.Methods/Principal FindingsIn this study, we show that disruption in mice of the Pxmp2 gene encoding Pxmp2, which belongs to a family of integral membrane proteins with unknown function, leads to partial restriction of peroxisomal membrane permeability to solutes in vitro and in vivo. Multiple-channel recording of liver peroxisomal preparations reveals that the channel-forming components with a conductance of 1.3 nS in 1.0 M KCl were lost in Pxmp2 −/− mice. The channel-forming properties of Pxmp2 were confirmed with recombinant protein expressed in insect cells and with native Pxmp2 purified from mouse liver. The Pxmp2 channel, with an estimated diameter of 1.4 nm, shows weak cation selectivity and no voltage dependence. The long-lasting open states of the channel indicate its functional role as a protein forming a general diffusion pore in the membrane.Conclusions/SignificancePxmp2 is the first peroxisomal channel identified, and its existence leads to prediction that the mammalian peroxisomal membrane is permeable to small solutes while transfer of “bulky” metabolites, e.g., cofactors (NAD/H, NADP/H, and CoA) and ATP, requires specific transporters.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Pxmp2 Is a Channel-Forming Protein in Mammalian Peroxisomal Membrane

et al. 2009

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“…Thus, these combined results strengthen the idea that the basis of the differential regulation of these genes during latency may lie within the sequence of the regulatory element itself. fungi, and viruses, and a recent report indicates that more than 10% of the genes in the human genome may be divergently transcribed from such promoters (9,17,19,27,36,42,51,(53)(54)(55)(56)(61)(62)(63). These regulatory sequences fall into two general categories.…”

Section: Vol 78 2004mentioning

confidence: 99%

The DNA Element Controlling Expression of the Varicella-Zoster Virus Open Reading Frame 28 and 29 Genes Consists of Two Divergent Unidirectional Promoters Which Have a Common USF Site

Yang

Hay

Ruyechan

2004

J Virol

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The mechanism of the divergent expression of the varicella-zoster virus (VZV) ORF 28 and ORF 29 genes from a common intergenic DNA element, the ORF 28/29 promoter, is of interest based on the observation that both genes are expressed during VZV lytic infection but only the ORF 29 gene is expressed in latently infected neurons. In the work presented here, expression driven by the ORF 28/29 intergenic region was examined. We found that the promoter activity towards the ORF 29 direction is more responsive to activation by the major viral transactivator IE62 than that towards the ORF 28 direction in the context of our experimental system. Analysis of the functional DNA elements involved in IE62 activation of the bidirectional ORF 28/29 regulatory element revealed that in both transfected and VZV-superinfected cells it is a fusion of two unidirectional promoters overlapping an essential USF binding site but with distinct TATA elements. A single TATA element directs expression in the ORF 28 direction, whereas the two TATA elements directing ORF 29 gene expression are alternatively and differentially utilized for transcription initiation. We also identified an Sp1 site localized proximal to the ORF 28 gene which functions as an activator element for expression in both directions. These results indicate that the ORF 28 and ORF 29 genes can be expressed either coordinately or independently and that the observed expression of only the ORF 29 gene during VZV latency may involve neuron-specific cellular factors and/or structural aspects of the latent viral genome.Varicella-zoster virus (VZV) is the causative agent of two human diseases: varicella (chickenpox) and zoster (shingles). Primary infection gives rise to varicella with characteristic skin lesions resulting from lytic infection of the virus in cutaneous epithelial cells. As a member of the neurotropic alphaherpesvirus subfamily, VZV can establish latency in the dorsal root ganglia following primary infection (4). Latent VZV DNA is predominantly localized in the neurons, although some researchers also identified viral sequences in nonneuronal satellite cells (14,22,23,32,37). Data obtained from human ganglia and animal models indicate that during latent infection, a small subset of lytic viral genes is expressed while most of the VZV genome is transcriptionally quiescent. These latency-expressed genes include open reading frames (ORFs) 63, 62, 29, 21, 4, and 66 (2, 7, 8, 11, 12, 20, 24, 33, 35, 66). In the majority of studies conducted, expression of these genes has been detected at the level of RNA. However, expression of all of these genes at the protein level has also been reported (8,12,33,35,66), raising the possibility of a role for one or more of them as trans-acting factors during latency. While the majority of the expressed proteins detected appear to be cytoplasmic rather than nuclear, the possibility of the presence of protein below the levels of detection in the nuclei or a rapid shuttling between the nucleus and cytoplasm cannot be discounted. Because s...

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“…Interestingly, TAP1 and LMP2, two genes that are critically involved in antigen presentation, have also been shown to be regulated by a bidirectional promoter (Wright et al, 1995). Other examples include BRCA1/NBR2 (Xu et al, 1997), DNA -PKcs/MCM4 (Connelly et al, 1998), DHFR/MSH3 (Shimada et al, 1989), G6PD/NEMO (Galgoczy et al, 2001), Ku86(KARP-1)/ TERP (Braastad et al, 2002), FEN1/C11orf10 , SAFB1/SAFB2 (Townson et al, 2003), HSP60/ HSP10 (Hansen et al, 2003), VLCAD/PSD-95 , Rap1/KARS (Tan et al, 2003), CaTin1/CaTin1-2 (Shin et al, 2003), and Pxmp2/PoleI (Otte et al, 2003).…”

Section: Discussionmentioning

confidence: 99%