Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants

Enuameh, Metewo Selase; Asriyan, Yuna; Richards, Adam; Christensen, Ryan; Hall, Victoria L.; Kazemian, Majid; Zhu, Cong; Pham, Hannah; Cheng, Qiong; Blatti, Charles; Brasefield, Jessie A.; Basciotta, Matthew D.; Ou, Jianhong; McNulty, Joseph C.; Zhu, Lihua Julie; Celniker, S; Sinha, Saurabh; Stormo, Gary D.; Brodsky, Michael; Wolfe, Scot A.

doi:10.1101/gr.151472.112

Cited by 72 publications

(102 citation statements)

References 111 publications

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“…Over the past decade, an extensive amount of information on binding preferences of TFs has been accumulated from in vitro and in vivo high-throughput binding assays (Harbison et al 2004;Berger et al 2008;Noyes et al 2008;Badis et al 2009;Wei et al 2010; The ENCODE Project Consortium 2012; Enuameh et al 2013;Jolma et al 2013;Nakagawa et al 2013;Yan et al 2013). Whereas these studies allow deriving consensus binding sites as well as PFMs of hundreds of TFs, both are insufficient for accurate identifications of the targets of a given TF within the genome.…”

Section: Discussionmentioning

confidence: 99%

“…However, selective binding of motifs by TFs has also been observed in a variety of in vitro experiments (Noyes et al 2008;Badis et al 2009;Berger and Bulyk 2009;Zhao et al 2009;Slattery et al 2011;Enuameh et al 2013;Gordân et al 2013;Jolma et al 2013;Afek et al 2014;Weirauch et al 2014;Abe et al 2015;Levo et al 2015). These in vitro studies show that TFs can bind to different sequences containing a similar motif with a large range of different affinities, which suggests that TF-DNA binding specificity is influenced by the DNA context surrounding the motif.…”

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confidence: 99%

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A widespread role of the motif environment in transcription factor binding across diverse protein families

et al. 2015

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Transcriptional regulation requires the binding of transcription factors (TFs) to short sequence-specific DNA motifs, usually located at the gene regulatory regions. Interestingly, based on a vast amount of data accumulated from genomic assays, it has been shown that only a small fraction of all potential binding sites containing the consensus motif of a given TF actually bind the protein. Recent in vitro binding assays, which exclude the effects of the cellular environment, also demonstrate selective TF binding. An intriguing conjecture is that the surroundings of cognate binding sites have unique characteristics that distinguish them from other sequences containing a similar motif that are not bound by the TF. To test this hypothesis, we conducted a comprehensive analysis of the sequence and DNA shape features surrounding the core-binding sites of 239 and 56 TFs extracted from in vitro HT-SELEX binding assays and in vivo ChIP-seq data, respectively. Comparing the nucleotide content of the regions around the TF-bound sites to the counterpart unbound regions containing the same consensus motifs revealed significant differences that extend far beyond the core-binding site. Specifically, the environment of the bound motifs demonstrated unique sequence compositions, DNA shape features, and overall high similarity to the core-binding motif. Notably, the regions around the binding sites of TFs that belong to the same TF families exhibited similar features, with high agreement between the in vitro and in vivo data sets. We propose that these unique features assist in guiding TFs to their cognate binding sites.

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Section: Discussionmentioning

confidence: 99%

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A widespread role of the motif environment in transcription factor binding across diverse protein families

et al. 2015

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“…In contrast, it is relatively straightforward to derive motifs from all of the common methods for in vitro analysis of TF sequence specificity, including Protein Binding Microarrays (PBMs), Bacterial 1-hybrid (B1H), and High-Throughput in vitro Selection (HT-SELEX) (Stormo and Zhao, 2010), all of which have been applied to hundreds of proteins (e.g. (Berger et al, 2008; Enuameh et al, 2013; Jolma et al, 2013; Noyes et al, 2008)).…”

Section: Introductionmentioning

confidence: 99%

Determination and Inference of Eukaryotic Transcription Factor Sequence Specificity

Weirauch

Yang

Albu

et al. 2014

Cell

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SUMMARY Transcription factor (TF) DNA sequence preferences direct their regulatory activity, but are currently known for only ~1% of all eukaryotic TFs. Broadly sampling DNA-binding domain (DBD) types from multiple eukaryotic clades, we determined DNA sequence preferences for >1,000 TFs encompassing 54 different DBD classes from 131 diverse eukaryotes. We find that closely related DBDs almost always have very similar DNA sequence preferences, enabling inference of motifs for ~34% of the ~170,000 known or predicted eukaryotic TFs. Sequences matching both measured and inferred motifs are enriched in ChIP-seq peaks and upstream of transcription start sites in diverse eukaryotic lineages. SNPs defining expression quantitative trait loci in Arabidopsis promoters are also enriched for predicted TF binding sites. Importantly, our motif “library” (http://cisbp.ccbr.utoronto.ca) can be used to identify specific TFs whose binding may be altered by human disease risk alleles. These data present a powerful resource for mapping transcriptional networks across eukaryotes.

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“…4F). There are two potential Glass binding sites (gl1 and gl2) within the genomic fragment that we used for making the reporter (Enuameh et al, 2013), which are evolutionarily conserved across different Drosophila species (Fig. 4D).…”

Section: Glass Activates Expression Of Transcription Factors Hazy Andmentioning

confidence: 99%

The transcription factor glass links eye field specification with photoreceptor differentiation in Drosophila

2016

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Eye development requires an evolutionarily conserved group of transcription factors, termed the retinal determination network (RDN). However, little is known about the molecular mechanism by which the RDN instructs cells to differentiate into photoreceptors. We show that photoreceptor cell identity in Drosophila is critically regulated by the transcription factor Glass, which is primarily expressed in photoreceptors and whose role in this process was previously unknown. Glass is both required and sufficient for the expression of phototransduction proteins. Our results demonstrate that the RDN member Sine oculis directly activates glass expression, and that Glass activates the expression of the transcription factors Hazy and Otd. We identified hazy as a direct target of Glass. Induced expression of Hazy in the retina partially rescues the glass mutant phenotype. Together, our results provide a transcriptional link between eye field specification and photoreceptor differentiation in Drosophila, placing Glass at a central position in this developmental process.

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Global analysis of Drosophila Cys₂-His₂ zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants

Cited by 72 publications

References 111 publications

A widespread role of the motif environment in transcription factor binding across diverse protein families

A widespread role of the motif environment in transcription factor binding across diverse protein families

Determination and Inference of Eukaryotic Transcription Factor Sequence Specificity

The transcription factor glass links eye field specification with photoreceptor differentiation in Drosophila

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