2.50
Hdl Handle:
http://hdl.handle.net/10033/246152
Title:
YY1-Binding Sites Provide Central Switch Functions in the PARP-1 Gene Expression Network.
Authors:
Doetsch, Martina; Gluch, Angela; Poznanović, Goran; Bode, Juergen; Vidaković, Melita
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.
Affiliation:
Helmholtz Centre for Infection Research/Epigenetic Regulation, Braunschweig, Germany.
Citation:
YY1-Binding Sites Provide Central Switch Functions in the PARP-1 Gene Expression Network. 2012, 7 (8):e44125 PLoS ONE
Journal:
PloS one
Issue Date:
2012
URI:
http://hdl.handle.net/10033/246152
DOI:
10.1371/journal.pone.0044125
PubMed ID:
22937159
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
Publications of RG Epigenetic Regulation Mechanisms (EPI)

Full metadata record

DC FieldValue Language
dc.contributor.authorDoetsch, Martinaen_GB
dc.contributor.authorGluch, Angelaen_GB
dc.contributor.authorPoznanović, Goranen_GB
dc.contributor.authorBode, Juergenen_GB
dc.contributor.authorVidaković, Melitaen_GB
dc.date.accessioned2012-09-27T13:01:41Z-
dc.date.available2012-09-27T13:01:41Z-
dc.date.issued2012-
dc.identifier.citationYY1-Binding Sites Provide Central Switch Functions in the PARP-1 Gene Expression Network. 2012, 7 (8):e44125 PLoS ONEen_GB
dc.identifier.issn1932-6203-
dc.identifier.pmid22937159-
dc.identifier.doi10.1371/journal.pone.0044125-
dc.identifier.urihttp://hdl.handle.net/10033/246152-
dc.description.abstractEvidence 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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to PloS oneen_GB
dc.titleYY1-Binding Sites Provide Central Switch Functions in the PARP-1 Gene Expression Network.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for Infection Research/Epigenetic Regulation, Braunschweig, Germany.en_GB
dc.identifier.journalPloS oneen_GB

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