Deciphering the DNA code for the function of the Drosophila polydactyl zinc finger protein Suppressor of Hairy-wing

Baxley, Ryan M.; Bullard, James D.; Klein, Michael W.; Fell, Ashley; Morales‐Rosado, Joel A.; Duan, Tingting; Geyer, Pamela

doi:10.1093/nar/gkx040

Cited by 35 publications

(57 citation statements)

References 61 publications

(112 reference statements)

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“…Almost a third of non-TSS PNAs contained the motif, suggesting that it might be a major determinant of nucleosome phasing. ''Motif 5'' is similar to a published consensus site for the insulator protein su(Hw) Baxley et al, 2017), which fits to our observation that su(Hw) binding profiles resemble the distribution of non-TSS Figure S2 and Table S2.…”

Section: A New Dna Motif Is Strongly Enriched At Non-tss Phased Regulsupporting

confidence: 84%

Genome-wide Rules of Nucleosome Phasing in Drosophila

Baldi¹,

Jain²,

Harpprecht³

et al. 2018

Molecular Cell

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Graphical Abstract Highlights d Phased nucleosome arrays are mapped genome-wide in Drosophila d A DNA motif strongly associated with phased arrays in flies and mice is identified d Phaser, a previously uncharacterized protein, binds this motif d Phased arrays are generated by local barrier elements and chromatin remodelers SUMMARY Regular successions of positioned nucleosomes, or phased nucleosome arrays (PNAs), are predominantly known from transcriptional start sites (TSSs). It is unclear whether PNAs occur elsewhere in the genome. To generate a comprehensive inventory of PNAs for Drosophila, we applied spectral analysis to nucleosome maps and identified thousands of PNAs throughout the genome. About half of them are not near TSSs and are strongly enriched for an uncharacterized sequence motif. Through genomewide reconstitution of physiological chromatin in Drosophila embryo extracts, we uncovered the molecular basis of PNA formation. We identified Phaser, an unstudied zinc finger protein that positions nucleosomes flanking the motif. It also revealed how the global activity of the chromatin remodelers CHRAC/ ACF, together with local barrier elements, generates islands of regular phasing throughout the genome. Our work demonstrates the potential of chromatin assembly by embryo extracts as a powerful tool to reconstitute chromatin features on a global scale in vitro.

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Section: A New Dna Motif Is Strongly Enriched At Non-tss Phased Regulsupporting

confidence: 84%

Genome-wide Rules of Nucleosome Phasing in Drosophila

Baldi¹,

Jain²,

Harpprecht³

et al. 2018

Molecular Cell

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show abstract

“…Almost a third of non-TSS PNA contained this motif, suggesting it might be a major determinant of nucleosome phasing outside of promoters. 'Motif 5' is very similar to a published consensus site for the insulator protein su(Hw) Baxley et al, 2017), which fits to our observation that su(Hw) binding profiles resemble the distribution of non-TSS PNA. The remaining motifs were predominantly signatures of relatively low complexity.…”

Section: A New Dna Motif Is Strongly Enriched At Non-tss Phased Regulsupporting

confidence: 86%

Genome-wide rules of nucleosome phasing

Baldi

Harpprecht

et al. 2016

Preprint

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Regular successions of positioned nucleosomes -phased nucleosome arrays (PNAs) -are predominantly known from transcriptional start sites (TSS). It is unclear whether PNAs occur elsewhere in the genome. To generate a comprehensive inventory of PNAs for Drosophila, we applied spectral analysis to nucleosome maps and identified thousands of PNAs throughout the genome. About half of them are not near TSS and strongly enriched for a novel sequence motif. Through genome-wide reconstitution of physiological chromatin in Drosophila embryo extracts we uncovered the molecular basis of PNA formation. We identified Phaser, an unstudied zinc finger protein that positions nucleosomes flanking the new motif. It also revealed how the global activity of the chromatin remodeler CHRAC/ACF, together with local barrier elements, generates islands of regular phasing throughout the genome. Our work demonstrates the potential of chromatin assembly by embryo extracts as a powerful tool to reconstitute chromatin features on a global scale in vitro.

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“…Finally, we note the possibility that some ZFs may engage with DNA in alternative binding modes that we have not yet characterized. A few C2H2-ZFPs are known to employ alternative sets of ZFs to bind to DNA [15][16][17] . This observation suggests that some ZFs might be engaged only in a subset of in vivo binding sites -such ZFs would not be part of the core motifs that we have presented in this paper, which can potentially explain their higher-than-random sequence specificity.…”

Section: Discussionmentioning

confidence: 99%

“…However, the binding sites of C2H2-ZFPs are often much shorter 12 , suggesting that only a fraction of the ZFs interact with the DNA while other ZFs might be involved in other functions such as mediating protein-protein 13 or protein-RNA 14 interactions. Currently, the DNAengaging ZFs of only a small subset of C2H2-ZFPs have been characterized [15][16][17] , preventing a comprehensive functional stratification of ZFs.…”

Section: Introductionmentioning

confidence: 99%

A domain-resolution map ofin vivoDNA binding reveals the regulatory consequences of somatic mutations in zinc finger transcription factors

Doğan

Kailasam

Corchado

et al. 2019

Preprint

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Multi-zinc finger proteins are the largest class of human transcription factors with integral roles in genome regulation and function. Often using a subset of their zinc finger domains, these proteins bind to diverse DNA sequences that make up the majority of the human regulatory lexicon. However, the molecular code that underlies the interaction of the zinc finger with DNA is incompletely understood, and for most multi-zinc finger proteins the zinc finger subset that is responsible for in vivo DNA binding is unknown. Here, we present a computational model, derived from a compendium of in vivo and in vitro binding preferences, that captures context-specific binding of zinc fingers to DNA. This model can predict the binding specificity of each zinc finger in its natural context more accurately than existing models, and together with molecular dynamics analyses reveals new structural aspects of DNA recognition by zinc finger proteins, including novel amino acid residues that contribute to sequence specificity. Furthermore, by combining this computational model with in vivo binding data, we identify the sequence preference of each protein and the zinc finger subset that is responsible for in vivo DNA binding, providing DNA binding maps and the associated domains for ~30% of all human multi-zinc finger proteins. We show that compared to non-DNA-binding zinc finger domains, DNA-binding zinc fingers are under stronger selective pressure across species and are depleted of genetic variants in the human population. Finally, we propose that a combination of context as well as intrinsic zinc finger features determines the ability to bind to DNA in vivo.

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Deciphering the DNA code for the function of the Drosophila polydactyl zinc finger protein Suppressor of Hairy-wing

Cited by 35 publications

References 61 publications

Genome-wide Rules of Nucleosome Phasing in Drosophila

Genome-wide Rules of Nucleosome Phasing in Drosophila

Genome-wide rules of nucleosome phasing

A domain-resolution map ofin vivoDNA binding reveals the regulatory consequences of somatic mutations in zinc finger transcription factors

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