ZifBASE: a database of zinc finger proteins and associated resources

Mannu, Jayakanthan; Muthukumaran, Jayaraman; Chandrasekar, Sanniyasi; Chawla, Konika; Punetha, Ankita; Sundar, Durai

doi:10.1186/1471-2164-10-421

Cited by 35 publications

(21 citation statements)

References 18 publications

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“…These amino acid positions are thus referred to as the zinc “fingerprint” amino acids (Figure 1A–C). A number of computational prediction tools have been developed to predict the specific DNA target sequences of zinc finger arrays that are based on several parameters: 1) the assumption of the collinearity of ZNF arrays, thus targeting DNA triplets without gaps, 2) the concept of zinc fingerprints controlling target specificity, and 3) experimental data of single zinc fingers within small zinc finger arrays bound to short DNA stretches [25–29]. However, growing evidence supports that not all the C2H2 domains within a zinc finger array bind DNA.…”

Section: Molecular Architecture Of Krab-zfpsmentioning

confidence: 99%

The Role of KRAB-ZFPs in Transposable Element Repression and Mammalian Evolution

2017

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Kruppel-associated box zinc finger proteins (KRAB-ZFPs) make up the largest family of transcription factors in humans. These proteins emerged in the last common ancestor of coelacanth and tetrapods and have expanded and diversified in the mammalian lineage. Although their mechanism of transcriptional repression has been well studied for over a decade, the DNA binding activities and the biological function of these proteins has been largely unexplored. Recent large scale ChIP-seq studies and loss-of-function experiments have revealed that KRAB-ZFPs play a major role in the recognition and transcriptional silencing of transposable elements (TEs), consistent with an “arms race model” of KRAB-ZFP evolution against invading TEs. However, this model is insufficient to explain the evolution of many KRAB-ZFPs that appear to domesticate TEs for novel host functions. We highlight some of the mammalian regulatory innovations driven by specific KRAB-ZFPs, including genomic imprinting, meiotic recombination hotspot choice, and placental growth.

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Section: Molecular Architecture Of Krab-zfpsmentioning

confidence: 99%

The Role of KRAB-ZFPs in Transposable Element Repression and Mammalian Evolution

2017

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“…bse.kyutech.ac.jp/jouhou/jouhoubank.html). Finally, we come to a database developed by our own team, ZifBASE (http://web.iitd.ac.in/*sundar/zifbase) a manually curated repository of information containing various natural and engineered zinc finger proteins collected from the Protein Data Bank, Mod Base, Protein Model Portal and from literature (Jayakanthan et al 2009). For natural zinc finger proteins, the name of the source organism for an entry is also stored.…”

Section: Computational Design Of Zfpmentioning

confidence: 99%

Re-programming DNA-binding specificity in zinc finger proteins for targeting unique address in a genome

et al. 2010

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Recent studies provide a glimpse of future potential therapeutic applications of custom-designed zinc finger proteins in achieving highly specific genomic manipulation. Custom-design of zinc finger proteins with tailor-made specificity is currently limited by the availability of information on recognition helices for all possible DNA targets. However, recent advances suggest that a combination of design and selection method is best suited to identify custom zinc finger DNA-binding proteins for known genome target sites. Design of functionally self-contained zinc finger proteins can be achieved by (a) modular protein engineering and (b) computational prediction. Here, we explore the novel functionality obtained by engineered zinc finger proteins and the computational approaches for prediction of recognition helices of zinc finger proteins that can raise our ability to re-program zinc finger proteins with desired novel DNA-binding specificities.

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“…Subsequently, MA has been used widely for many applications. There are plethora of tools reported in the literature that are based on assuming modular mode of binding at the molecular level, including - OPEN [13], ZiFiT [14], Zif-Predict [15], ZifBASE [16]. …”

Section: Introductionmentioning

confidence: 99%

Exploiting the recognition code for elucidating the mechanism of zinc finger protein-DNA interactions

2016

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BackgroundEngineering zinc finger protein motifs for specific binding to double-stranded DNA is critical for targeted genome editing. Most existing tools for predicting DNA-binding specificity in zinc fingers are trained on data obtained from naturally occurring proteins, thereby skewing the predictions. Moreover, these mostly neglect the cooperativity exhibited by zinc fingers.MethodsHere, we present an ab-initio method that is based on mutation of the key α-helical residues of individual fingers of the parent template for Zif-268 and its consensus sequence (PDB ID: 1AAY). In an attempt to elucidate the mechanism of zinc finger protein-DNA interactions, we evaluated and compared three approaches, differing in the amino acid mutations introduced in the Zif-268 parent template, and the mode of binding they try to mimic, i.e., modular and synergistic mode of binding.ResultsComparative evaluation of the three strategies reveals that the synergistic mode of binding appears to mimic the ideal mechanism of DNA-zinc finger protein binding. Analysis of the predictions made by all three strategies indicate strong dependence of zinc finger binding specificity on the amino acid propensity and the position of a 3-bp DNA sub-site in the target DNA sequence. Moreover, the binding affinity of the individual zinc fingers was found to increase in the order Finger 1 < Finger 2 < Finger 3, thus confirming the cooperative effect.ConclusionsOur analysis offers novel insights into the prediction of ZFPs for target DNA sequences and the approaches have been made available as an easy to use web server at http://web.iitd.ac.in/~sundar/zifpredict_ihbe Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3324-8) contains supplementary material, which is available to authorized users.

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ZifBASE: a database of zinc finger proteins and associated resources

Cited by 35 publications

References 18 publications

The Role of KRAB-ZFPs in Transposable Element Repression and Mammalian Evolution

The Role of KRAB-ZFPs in Transposable Element Repression and Mammalian Evolution

Re-programming DNA-binding specificity in zinc finger proteins for targeting unique address in a genome

Exploiting the recognition code for elucidating the mechanism of zinc finger protein-DNA interactions

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