YY1-binding sites provide central switch functions in the PARP-1 gene expression network.

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...

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Autores principales: Martina Doetsch, Angela Gluch, Goran Poznanović, Juergen Bode, Melita Vidaković
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:b01a463362f2489684330bdf098c904b2021-11-18T07:07:25ZYY1-binding sites provide central switch functions in the PARP-1 gene expression network.1932-620310.1371/journal.pone.0044125https://doaj.org/article/b01a463362f2489684330bdf098c904b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22937159/?tool=EBIhttps://doaj.org/toc/1932-6203Evidence 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.Martina DoetschAngela GluchGoran PoznanovićJuergen BodeMelita VidakovićPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e44125 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Martina Doetsch
Angela Gluch
Goran Poznanović
Juergen Bode
Melita Vidaković
YY1-binding sites provide central switch functions in the PARP-1 gene expression network.
description 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.
format article
author Martina Doetsch
Angela Gluch
Goran Poznanović
Juergen Bode
Melita Vidaković
author_facet Martina Doetsch
Angela Gluch
Goran Poznanović
Juergen Bode
Melita Vidaković
author_sort Martina Doetsch
title YY1-binding sites provide central switch functions in the PARP-1 gene expression network.
title_short YY1-binding sites provide central switch functions in the PARP-1 gene expression network.
title_full YY1-binding sites provide central switch functions in the PARP-1 gene expression network.
title_fullStr YY1-binding sites provide central switch functions in the PARP-1 gene expression network.
title_full_unstemmed YY1-binding sites provide central switch functions in the PARP-1 gene expression network.
title_sort yy1-binding sites provide central switch functions in the parp-1 gene expression network.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/b01a463362f2489684330bdf098c904b
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AT angelagluch yy1bindingsitesprovidecentralswitchfunctionsintheparp1geneexpressionnetwork
AT goranpoznanovic yy1bindingsitesprovidecentralswitchfunctionsintheparp1geneexpressionnetwork
AT juergenbode yy1bindingsitesprovidecentralswitchfunctionsintheparp1geneexpressionnetwork
AT melitavidakovic yy1bindingsitesprovidecentralswitchfunctionsintheparp1geneexpressionnetwork
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