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Abstract
The important regulatory role of the guanine-quadruplex (GQ) structure, present in the nuclease hypersensitive element (NHE) III1 region of the human c-myc (h c-myc) gene's promoter, in the regulation of the transcription of that gene has been documented. Here we present evidences, that the human nuclear poly(ADP-ribose)polymerase-1 (h PARP-1) protein participates in the regulation of the h c-myc gene expression through its interaction with this GQ structure, characterized by binding assays, fluorescence energy transfer (FRET) experiments and by affinity pull-down experiments in vitro, and by chromatin immunoprecipitation (ChIP)-qPCR analysis and h c-myc-promoter-luciferase reporter determinations in vivo. We surmise that h PARP-1 binds to the GQ structure and participates in the conversion of that structure into the transcriptionally more active B-DNA form. The first Zn-finger structure present in h PARP-1 participates in this interaction. PARP-1 might be a new member of the group of proteins participating in the regulation of transcription through their interactions with GQ structures present in the promoters of different genes.
Highlights
The GQ non-B-DNA structure is built up from two or more parallel guanine-tetrad layers, each containing four guanine units held together by Hoogsteen base pairing [1]
Because PARP-1 was shown to bind to the base part of the cruciform structure [25], we carried experiments to show, whether h PARP-1 binding to the wild type h c-myc GQ structure is influenced by TMPyP4
In this publication we present experimental evidence suggesting that h PARP-1 participates in the regulation of the transcription of the h c-myc gene
Summary
The GQ non-B-DNA structure is built up from two or more parallel guanine-tetrad layers, each containing four guanine units held together by Hoogsteen base pairing [1]. The GQ structure first has been found in telomers but recently in silico estimations predict their total number in the whole genome to be around 350 000 units [2]. Genes with high biological importance as c-myc, K- and Nras, ret, met, myb, ets, vegf or hif1A contain GQ structures in their promoters [3,4,5,6,7]. Experiments have proven their existence and structure and their modus operandi in the regulation of transcription in vitro, but much less is known about their role and importance in the regulation of transcription in vivo.
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