YY1-Binding Sites Provide Central Switch Functions in the PARP-1 Gene Expression Network.
dc.contributor.author | Doetsch, Martina | |
dc.contributor.author | Gluch, Angela | |
dc.contributor.author | Poznanović, Goran | |
dc.contributor.author | Bode, Juergen | |
dc.contributor.author | Vidaković, Melita | |
dc.date.accessioned | 2012-09-27T13:01:41Z | |
dc.date.available | 2012-09-27T13:01:41Z | |
dc.date.issued | 2012 | |
dc.identifier.citation | YY1-Binding Sites Provide Central Switch Functions in the PARP-1 Gene Expression Network. 2012, 7 (8):e44125 PLoS ONE | en_GB |
dc.identifier.issn | 1932-6203 | |
dc.identifier.pmid | 22937159 | |
dc.identifier.doi | 10.1371/journal.pone.0044125 | |
dc.identifier.uri | http://hdl.handle.net/10033/246152 | |
dc.description.abstract | Evidence is presented for the involvement of the interplay between transcription factor Yin Yang 1 (YY1) and poly(ADP-ribose) polymerase-1 (PARP-1) in the regulation of mouse PARP-1 gene (muPARP-1) promoter activity. We identified potential YY1 binding motifs (BM) at seven positions in the muPARP-1 core-promoter (-574/+200). Binding of YY1 was observed by the electrophoretic supershift assay using anti-YY1 antibody and linearized or supercoiled forms of plasmids bearing the core promoter, as well as with 30 bp oligonucleotide probes containing the individual YY1 binding motifs and four muPARP-1 promoter fragments. We detected YY1 binding to BM1 (-587/-558), BM4 (-348/-319) and a very prominent association with BM7 (+86/+115). Inspection of BM7 reveals overlap of the muPARP-1 translation start site with the Kozak sequence and YY1 and PARP-1 recognition sites. Site-directed mutagenesis of the YY1 and PARP-1 core motifs eliminated protein binding and showed that YY1 mediates PARP-1 binding next to the Kozak sequence. Transfection experiments with a reporter gene under the control of the muPARP-1 promoter revealed that YY1 binding to BM1 and BM4 independently repressed the promoter. Mutations at these sites prevented YY1 binding, allowing for increased reporter gene activity. In PARP-1 knockout cells subjected to PARP-1 overexpression, effects similar to YY1 became apparent; over expression of YY1 and PARP-1 revealed their synergistic action. Together with our previous findings these results expand the PARP-1 autoregulatory loop principle by YY1 actions, implying rigid limitation of muPARP-1 expression. The joint actions of PARP-1 and YY1 emerge as important contributions to cell homeostasis. | |
dc.language.iso | en | en |
dc.rights | Archived with thanks to PloS one | en_GB |
dc.title | YY1-Binding Sites Provide Central Switch Functions in the PARP-1 Gene Expression Network. | en |
dc.type | Article | en |
dc.contributor.department | Helmholtz Centre for Infection Research/Epigenetic Regulation, Braunschweig, Germany. | en_GB |
dc.identifier.journal | PloS one | en_GB |
refterms.dateFOA | 2018-06-13T17:08:04Z | |
html.description.abstract | Evidence is presented for the involvement of the interplay between transcription factor Yin Yang 1 (YY1) and poly(ADP-ribose) polymerase-1 (PARP-1) in the regulation of mouse PARP-1 gene (muPARP-1) promoter activity. We identified potential YY1 binding motifs (BM) at seven positions in the muPARP-1 core-promoter (-574/+200). Binding of YY1 was observed by the electrophoretic supershift assay using anti-YY1 antibody and linearized or supercoiled forms of plasmids bearing the core promoter, as well as with 30 bp oligonucleotide probes containing the individual YY1 binding motifs and four muPARP-1 promoter fragments. We detected YY1 binding to BM1 (-587/-558), BM4 (-348/-319) and a very prominent association with BM7 (+86/+115). Inspection of BM7 reveals overlap of the muPARP-1 translation start site with the Kozak sequence and YY1 and PARP-1 recognition sites. Site-directed mutagenesis of the YY1 and PARP-1 core motifs eliminated protein binding and showed that YY1 mediates PARP-1 binding next to the Kozak sequence. Transfection experiments with a reporter gene under the control of the muPARP-1 promoter revealed that YY1 binding to BM1 and BM4 independently repressed the promoter. Mutations at these sites prevented YY1 binding, allowing for increased reporter gene activity. In PARP-1 knockout cells subjected to PARP-1 overexpression, effects similar to YY1 became apparent; over expression of YY1 and PARP-1 revealed their synergistic action. Together with our previous findings these results expand the PARP-1 autoregulatory loop principle by YY1 actions, implying rigid limitation of muPARP-1 expression. The joint actions of PARP-1 and YY1 emerge as important contributions to cell homeostasis. |