Phylogenomic analysis of the emergence of GC-rich transcription elements

Khuu, Patricia; Maurice, Sandor; DeYoung, Jennifer; Ho, P Shing

doi:10.1073/pnas.0707203104

Cited by 49 publications

(43 citation statements)

References 26 publications

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“…SIBZ analysis has found an enrichment of regions with Z-forming potential around transcription start sites (TSSs) [31]. Other less rigorous methods, such as Z-Catcher and Z-Hunt , have found qualitatively similar patterns of Z-DNA enrichment around TSSs [31], [55], [69], [70], although they find different numbers of sites than we do. Here we examine how superhelical B-Z transitions compete with denaturation at these locations, as well as in the regions where transcription terminates.…”

Section: Resultsmentioning

confidence: 41%

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Theoretical Analysis of Competing Conformational Transitions in Superhelical DNA

Zhabinskaya

Benham²

2012

PLoS Comput Biol

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We develop a statistical mechanical model to analyze the competitive behavior of transitions to multiple alternate conformations in a negatively supercoiled DNA molecule of kilobase length and specified base sequence. Since DNA superhelicity topologically couples together the transition behaviors of all base pairs, a unified model is required to analyze all the transitions to which the DNA sequence is susceptible. Here we present a first model of this type. Our numerical approach generalizes the strategy of previously developed algorithms, which studied superhelical transitions to a single alternate conformation. We apply our multi-state model to study the competition between strand separation and B-Z transitions in superhelical DNA. We show this competition to be highly sensitive to temperature and to the imposed level of supercoiling. Comparison of our results with experimental data shows that, when the energetics appropriate to the experimental conditions are used, the competition between these two transitions is accurately captured by our algorithm. We analyze the superhelical competition between B-Z transitions and denaturation around the c-myc oncogene, where both transitions are known to occur when this gene is transcribing. We apply our model to explore the correlation between stress-induced transitions and transcriptional activity in various organisms. In higher eukaryotes we find a strong enhancement of Z-forming regions immediately 5′ to their transcription start sites (TSS), and a depletion of strand separating sites in a broad region around the TSS. The opposite patterns occur around transcript end locations. We also show that susceptibility to each type of transition is different in eukaryotes and prokaryotes. By analyzing a set of untranscribed pseudogenes we show that the Z-susceptibility just downstream of the TSS is not preserved, suggesting it may be under selection pressure.

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Section: Resultsmentioning

confidence: 41%

“…There has been previous evidence of depletion of Z-form DNA around TSS of prokaryotic genomes [69], [73]. Here we investigate these properties together by using the BDZ trans algorithm to analyze the average transition behavior of 4456 E. coli gene sequences.…”

Section: Resultsmentioning

confidence: 99%

Theoretical Analysis of Competing Conformational Transitions in Superhelical DNA

Zhabinskaya

Benham²

2012

PLoS Comput Biol

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“…The GT:AC repeats are estimated to account for more than 0.25% of the entire human genome [35]. A computer-based thermodynamic search strategy (Z-Hunt-II) used by the Ho group to analyze the complete human genome showed that Z-DNA-forming sequences occur approximately once every 3,000 bp [70]. Furthermore, Z-DNA-forming regions were found to be distinctly located near the 5’ ends of genes in the genome, and the proximity between these regions and the transcription start sites became more pronounced during the divergence from prokaryotes to eukaryotes [70].…”

Section: Genome-wide Analyses and Evolutionary Relationshipsmentioning

confidence: 99%

“…A computer-based thermodynamic search strategy (Z-Hunt-II) used by the Ho group to analyze the complete human genome showed that Z-DNA-forming sequences occur approximately once every 3,000 bp [70]. Furthermore, Z-DNA-forming regions were found to be distinctly located near the 5’ ends of genes in the genome, and the proximity between these regions and the transcription start sites became more pronounced during the divergence from prokaryotes to eukaryotes [70]. Therefore, the location bias of these GT:AC repeats is supportive of Z-DNA formation and stabilization by the transient surges in negative supercoiling associated with transcription.…”

Section: Genome-wide Analyses and Evolutionary Relationshipsmentioning

confidence: 99%

Non-B DNA structure-induced genetic instability and evolution

Zhao

Bacolla

Wang

et al. 2009

Cell. Mol. Life Sci.

364

333

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Repetitive DNA motifs are abundant in the genomes of various species and have the capacity to adopt non-canonical (i.e. non-B) DNA structures. Several non-B DNA structures, including cruciforms, slipped structures, triplexes, G-quadruplexes, and Z-DNA, have been shown to cause mutations, such as deletions, expansions, and translocations in both prokaryotes and eukaryotes. Their distributions in genomes are not random and often co-localize with sites of chromosomal breakage associated with genetic diseases. Current genome-wide sequence analyses suggest that the genomic instabilities induced by non-B DNA structure-forming sequences not only result in predisposition to disease, but also contribute to rapid evolutionary changes, particularly in genes associated with development and regulatory functions. In this review, we describe the occurrence of non-B DNA-forming sequences in various species, the classes of genes enriched in non-B DNA-forming sequences, and recent mechanistic studies on DNA structure-induced genomic instability to highlight their importance in genomes.

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“…The authors suggested that Z-DNA upstream of the nuclear factor-1 binding site helped to maintain the gene in its activated, nucleosome-free state (nucleosomes do not bind to the very rigid Z-DNA form (Ausio et al, 1987)). In support of its potential role in the regulation of eukaryotic genes, we have found that Z-forming sequences accumulate near the transcription start site of genes in humans and other eukaryotes (Khuu et al, 2007;Schroth et al, 1992), and that ~80% of the genes in human chromosome 22 have at least one Z-DNA sequence in the vicinity of their transcription start sites (Champ et al, 2004). The discovery of protein domains having very high specificity for Z-DNA (Rich and Zhang, 2003), in some cases with nanomolar K D 's, have suggested additional functions that include, for example, RNA editing and gene transactivation.…”

Section: Z-dnamentioning

confidence: 99%