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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2012
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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) |
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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 |
work_keys_str_mv |
AT martinadoetsch yy1bindingsitesprovidecentralswitchfunctionsintheparp1geneexpressionnetwork AT angelagluch yy1bindingsitesprovidecentralswitchfunctionsintheparp1geneexpressionnetwork AT goranpoznanovic yy1bindingsitesprovidecentralswitchfunctionsintheparp1geneexpressionnetwork AT juergenbode yy1bindingsitesprovidecentralswitchfunctionsintheparp1geneexpressionnetwork AT melitavidakovic yy1bindingsitesprovidecentralswitchfunctionsintheparp1geneexpressionnetwork |
_version_ |
1718423935207342080 |