ZIFIBI: Prediction of DNA binding sites for zinc finger proteins

Cho, Soo Young; Chung, Myungguen; Park, Minyoung; Park, Sung Jin; Lee, Young Seek

doi:10.1016/j.bbrc.2008.02.106

Cited by 31 publications

(12 citation statements)

References 21 publications

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“…The identification of Zfp37 genes suggests that ZF genes are generally involved in the complex pathways from round spermatids to spermatozoa in mitten crab. Furthermore, it is also the first time Zfp37 genes have been found to participate in the processes of spermatogenesis and sex maturity in crustaceans (Sepp and Choo, 2005; Cho et al , 2008), although their specific function in sperm development needs to be further examined.…”

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confidence: 99%

A transcriptome analysis of mitten crab testes (Eriocheir sinensis)

et al. 2010

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The identification of expressed genes involved in sexual precocity of the mitten crab (Eriocheir sinensis) is critical for a better understanding of its reproductive development. To this end, we constructed a cDNA library from the rapid developmental stage of testis of E. sinensis and sequenced 3,388 randomly picked clones. After processing, 2,990 high-quality expressed sequence tags (ESTs) were clustered into 2,415 unigenes including 307 contigs and 2,108 singlets, which were then compared to the NCBI non-redundant (nr) protein and nucleotide (nt) database for annotation with Blastx and Blastn, respectively. After further analysis, 922 unigenes were obtained with concrete annotations and 30 unigenes were found to have functions possibly related to the process of reproduction in male crabs – six transcripts relevant to spermatogenesis (especially Cyclin K and RecA homolog DMC1), two transcripts involved in nuclear protein transformation, two heat-shock protein genes, eleven transcription factor genes (a series of zinc-finger proteins), and nine cytoskeleton protein-related genes. Our results, besides providing valuable information related to crustacean reproduction, can also serve as a base for future studies of reproductive and developmental biology.

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confidence: 99%

A transcriptome analysis of mitten crab testes (Eriocheir sinensis)

et al. 2010

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“…Even for species in which PRDM9 is known to determine recombination hotspots, the specific DNA motifs may not be clear, due to various reasons such as rapid evolution and extensive diversity of PRDM9 zinc finger arrays, variation of genetic and epigenetic contexts flanking the binding sites of PRDM9. In [13], for example, although a consensus motif was found to be present in at least 73% of mouse hotspots, the consensus motif is not the same as the putative PRDM9 binding site generated by ZIFIBI database [23] from zinc fingers in the PRDM9 protein. Moreover, for human and mouse, some transcription factor binding sites in addition to the PRDM9 motif may also regulate recombination hotspots [24,10].…”

Section: Resultsmentioning

confidence: 99%

LDsplit: screening for cis-regulatory motifs stimulating meiotic recombination hotspots by analysis of DNA sequence polymorphisms

Yang

Guo

et al. 2014

BMC Bioinformatics

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BackgroundAs a fundamental genomic element, meiotic recombination hotspot plays important roles in life sciences. Thus uncovering its regulatory mechanisms has broad impact on biomedical research. Despite the recent identification of the zinc finger protein PRDM9 and its 13-mer binding motif as major regulators for meiotic recombination hotspots, other regulators remain to be discovered. Existing methods for finding DNA sequence motifs of recombination hotspots often rely on the enrichment of co-localizations between hotspots and short DNA patterns, which ignore the cross-individual variation of recombination rates and sequence polymorphisms in the population. Our objective in this paper is to capture signals encoded in genetic variations for the discovery of recombination-associated DNA motifs.ResultsRecently, an algorithm called “LDsplit” has been designed to detect the association between single nucleotide polymorphisms (SNPs) and proximal meiotic recombination hotspots. The association is measured by the difference of population recombination rates at a hotspot between two alleles of a candidate SNP. Here we present an open source software tool of LDsplit, with integrative data visualization for recombination hotspots and their proximal SNPs. Applying LDsplit on SNPs inside an established 7-mer motif bound by PRDM9 we observed that SNP alleles preserving the original motif tend to have higher recombination rates than the opposite alleles that disrupt the motif. Running on SNP windows around hotspots each containing an occurrence of the 7-mer motif, LDsplit is able to guide the established motif finding algorithm of MEME to recover the 7-mer motif. In contrast, without LDsplit the 7-mer motif could not be identified.ConclusionsLDsplit is a software tool for the discovery of cis-regulatory DNA sequence motifs stimulating meiotic recombination hotspots by screening and narrowing down to hotspot associated SNPs. It is the first computational method that utilizes the genetic variation of recombination hotspots among individuals, opening a new avenue for motif finding. Tested on an established motif and simulated datasets, LDsplit shows promise to discover novel DNA motifs for meiotic recombination hotspots.

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“…We also compared our structure-based approach with three previously described and publicly accessible algorithms for predicting ZF–DNA interactions: a structure-based approach incorporating family-specific amino acid–nucleotide interaction preferences learned from experimental binding data [‘Kaplan05’ (30)]; Zinc Finger Binding site database (ZIFIBI), which uses a hidden Markov model to generate binding site predictions (31); and a recent machine learning approach that incorporates data on binding and non-binding DNA sites through the use of a support vector machine [‘Persikov09’ (33)]. Given that experimental binding data for the proteins of known structure were likely used to train one or more of these methods, we restricted our comparison to the six ZF proteins without solved structures whose specificities were recently profiled by protein binding microarrays (49).…”

Section: Resultsmentioning

confidence: 99%

Extensive protein and DNA backbone sampling improves structure-based specificity prediction for C2H2 zinc fingers

Yanover

Bradley

2011

Nucleic Acids Research

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Sequence-specific DNA recognition by gene regulatory proteins is critical for proper cellular functioning. The ability to predict the DNA binding preferences of these regulatory proteins from their amino acid sequence would greatly aid in reconstruction of their regulatory interactions. Structural modeling provides one route to such predictions: by building accurate molecular models of regulatory proteins in complex with candidate binding sites, and estimating their relative binding affinities for these sites using a suitable potential function, it should be possible to construct DNA binding profiles. Here, we present a novel molecular modeling protocol for protein-DNA interfaces that borrows conformational sampling techniques from de novo protein structure prediction to generate a diverse ensemble of structural models from small fragments of related and unrelated protein-DNA complexes. The extensive conformational sampling is coupled with sequence space exploration so that binding preferences for the target protein can be inferred from the resulting optimized DNA sequences. We apply the algorithm to predict binding profiles for a benchmark set of eleven C2H2 zinc finger transcription factors, five of known and six of unknown structure. The predicted profiles are in good agreement with experimental binding data; furthermore, examination of the modeled structures gives insight into observed binding preferences.

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ZIFIBI: Prediction of DNA binding sites for zinc finger proteins

Cited by 31 publications

References 21 publications

A transcriptome analysis of mitten crab testes (Eriocheir sinensis)

A transcriptome analysis of mitten crab testes (Eriocheir sinensis)

LDsplit: screening for cis-regulatory motifs stimulating meiotic recombination hotspots by analysis of DNA sequence polymorphisms

Extensive protein and DNA backbone sampling improves structure-based specificity prediction for C2H2 zinc fingers

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