Homodimeric MyoD Preferentially Binds Tetraplex Structures of Regulatory Sequences of Muscle-specific Genes

Etzioni, Shulamit; Yafe, Anat; Khateb, Samer; Weisman-Shomer, Pnina; Bengal, Eyal; Fry, Michael

doi:10.1074/jbc.m500820200

Cited by 38 publications

(65 citation statements)

References 49 publications

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“…It must be noted that our conclusions are based on mostly predicted transcription-factor-binding sites and unlike the human c-myc and other cases (where G4 is implicated to be regulatory) (Howell et al 1996;Siddiqui-Jain et al 2002;Etzioni et al 2005), no experimental proof exists of G4 DNA-mediated regulation in bacteria. Genome-wide ChIP analysis for bind- ing sites in conjunction with molecules or factors that specifically bind to G4 motifs and in vitro specificity assays will be required to confirm our findings (Schaffitzel et al 2001;Rezler et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide prediction of G4 DNA as regulatory motifs: Role inEscherichia coliglobal regulation

Rawal¹,

Kummarasetti²,

Ravindran³

et al. 2006

Genome Res.

307

335

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The role of nonlinear DNA in replication, recombination, and transcription has become evident in recent years. Although several studies have predicted and characterized regulatory elements at the sequence level, very few have investigated DNA structure as regulatory motifs. Here, using G-quadruplex or G4 DNA motifs as a model, we have researched the role of DNA structure in transcription on a genome-wide scale. Analyses of >61,000 open reading frames (ORFs) across 18 prokaryotes show enrichment of G4 motifs in regulatory regions and indicate its predominance within promoters of genes pertaining to transcription, secondary metabolite biosynthesis, and signal transduction. Based on this, we predict that G4 DNA may present regulatory signals. This is supported by conserved G4 motifs in promoters of orthologous genes across phylogenetically distant organisms. We hypothesized a regulatory role of G4 DNA during supercoiling stress, when duplex destabilization may result in G4 formation. This is in line with our observations from target site analysis for 55 DNA-binding proteins in Escherichia coli, which reveals significant (P < 0.001) association of G4 motifs with target sites of global regulators FIS and Lrp and the sigma factor RpoD ( 70 ). These factors together control >1000 genes in the early growth phase and are believed to be induced by supercoiled DNA. We also predict G4 motif-induced supercoiling sensitivity for >30 operons in E. coli, and our findings implicate G4 DNA in DNA-topology-mediated global gene regulation in E. coli.

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Section: Discussionmentioning

confidence: 99%

Genome-wide prediction of G4 DNA as regulatory motifs: Role inEscherichia coliglobal regulation

Rawal¹,

Kummarasetti²,

Ravindran³

et al. 2006

Genome Res.

307

335

View full text Add to dashboard Cite

show abstract

“…Homodimers of MyoD are known to form, but these bind DNA with much lower affinity and do not function as efficient trans-activators compared with heterodimers. It is now apparent that MyoD homodimers preferentially bind to G4 DNA, suggesting that homodimers may negatively regulate muscle gene expression by binding to G4 DNA, whereas heterodimers bind avidly to E-boxes and lead to an up-regulation in transcription [112]. The close juxtaposition of an E-box to a G4 region in sMtCK also raises the possibility that G4 DNA-forming regions may act as micro-environments for the recruitment of tissue-restricted factors such as MyoD, which could then be displaced by the ubiquitous E2 proteins to form positive-acting heterodimers that migrate onto an adjacent E-box [113].…”

Section: Relevance Of G4 Dna To Cardiovascular Biologymentioning

confidence: 98%

G-Quadruplexes—Novel Mediators of Gene Function

Zhou

Brand

Ying

2011

J. of Cardiovasc. Trans. Res.

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Since the famous double-helix model was proposed, chromosomal DNA has been regarded as a rigid molecule containing the genetic information of an organism. It is clear now that DNA can adopt many transient, complex structures that can perform different biological functions. The G4 DNA (also called DNA G-quadruplex or G-tetraplex), a four-stranded DNA structure composed of stacked G-tetrads (guanine tetrads), has attracted much attention during the past two decades due to its ability to adopt a variety of structures and its possible biological functions. This review gives a glimpse on the structural diversity and biophysical properties of these fascinating DNA structures. Common methods that are widely used in investigating biophysical properties and biological functions of G4 DNA are described briefly. Next, bioinformatics studies that indicate evidence of evolutionary selection and potential functions of G4 DNA are discussed. Finally, examples of various biological functions of different G4 DNA are given, and potential roles of G4 DNA in respect of cardiovascular science are discussed.

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“…In the case of loci with QFP located downstream of the promoter and on the sense strand, the binding of NMM to G4-RNA structures in mRNA transcripts might allow for their stabilization. A second manipulation, deletion of the SGS1 gene, which encodes a G4-DNAunwinding helicase, caused preferential downregulation of loci with QFP in their ORFs [77,78]. Remarkably, this association was particularly true for the template strand, raising the possibility that quadruplexes unresolved by Sgs1p provide an impediment progression of RNA polymerase.…”

Section: G-quadruplexes and Transcriptionmentioning

confidence: 99%

In vivo veritas: Using yeast to probe the biological functions of G-quadruplexes

et al. 2008

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Certain guanine-rich sequences are capable of forming higher order structures known as Gquadruplexes. Moreover, particular genomic regions in a number of highly divergent organisms are enriched for such sequences, raising the possibility that G-quadruplexes form in vivo and affect cellular processes. While G-quadruplexes have been rigorously studied in vitro, whether these structures actually form in vivo and what their roles might be in the context of the cell have remained largely unanswered questions. Recent studies suggest that G-quadruplexes participate in the regulation of such varied processes as telomere maintenance, transcriptional regulation and ribosome biogenesis. Here we review studies aimed at elucidating the in vivo functions of quadruplex structures, with a particular focus on findings in yeast. In addition, we discuss the utility of yeast model systems in the study of the cellular roles of G-quadruplexes.

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Homodimeric MyoD Preferentially Binds Tetraplex Structures of Regulatory Sequences of Muscle-specific Genes

Cited by 38 publications

References 49 publications

Genome-wide prediction of G4 DNA as regulatory motifs: Role inEscherichia coliglobal regulation

Genome-wide prediction of G4 DNA as regulatory motifs: Role inEscherichia coliglobal regulation

G-Quadruplexes—Novel Mediators of Gene Function

In vivo veritas: Using yeast to probe the biological functions of G-quadruplexes

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