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dc.creatorMarković, Jelena
dc.creatorGrdović, Nevena
dc.creatorDinić, Svetlana
dc.creatorKaran-Djurašević, Teodora
dc.creatorUskoković, Aleksandra
dc.creatorArambašić Jovanović, Jelena
dc.creatorMihailović, Mirjana
dc.creatorPavlović, Sonja
dc.creatorPoznanović, Goran
dc.creatorVidaković, Melita
dc.date.accessioned2018-11-26T14:06:42Z
dc.date.available2018-11-26T14:06:42Z
dc.date.issued2013
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/pubmed/23555743
dc.identifier.urihttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3608566
dc.identifier.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.
dc.identifier.urihttps://ibiss-r.rcub.bg.ac.rs/handle/123456789/3186
dc.description.abstractDespite significant progress, the molecular mechanisms responsible for pancreatic beta cell depletion and development of diabetes remain poorly defined. At present, there is no preventive measure against diabetes. The positive impact of CXCL12 expression on the pancreatic beta cell prosurvival phenotype initiated this study. Our aim was to provide novel insight into the regulation of rat CXCL12 gene (Cxcl12) transcription. The roles of poly(ADP-ribose) polymerase-1 (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation. The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression. Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription. Streptozotocin (STZ)-induced general toxicity in pancreatic beta cells was followed by changes in Cxcl12 promoter regulation. PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression. During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding. These interactions were accompanied by Cxcl12 downregulation. In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1. These interactions resulted in higher Cxcl12 expression. The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the functional interplay of these proteins could finely balance Cxcl12 transcription.
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173020/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41004/RS//
dc.rightsopenAccess
dc.sourcePLOS One
dc.titlePARP-1 and YY1 Are Important Novel Regulators of CXCL12 Gene Transcription in Rat Pancreatic Beta Cells
dc.typearticleen
dc.rights.licenseBY
dcterms.abstractВидаковић, Мелита; Грдовић, Невена; Динић, Светлана; Ускоковић, Aлександра; Aрамбашић, Јелена; Михаиловић, Мирјана; Павловић, Соња; Познановић, Горан; Марковић, Јелена; Каран-Дјурашевић, Теодора;
dc.rights.holder© 2013 Marković et al.
dc.citation.issue3
dc.citation.volume8
dc.identifier.doi10.1371/journal.pone.0059679
dc.identifier.pmid23555743
dc.identifier.scopus2-s2.0-84875465346
dc.identifier.wos000317418500074
dc.citation.spagee59679
dc.type.versionpublishedVersionen


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