Genome-wide polycomb target gene prediction in Drosophila melanogaster

Zeng, Jia; Kirk, Brian D.; Gou, Yufeng; Wang, Qinghua; Ma, Jianpeng

doi:10.1093/nar/gks209

Cited by 27 publications

(29 citation statements)

References 104 publications

(164 reference statements)

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“…Algorithms based on clustered consensus binding sites for PRE DNA binding proteins have been marginally successful in identifying PREs, giving both false positive and false negative results (Fiedler & Rehmsmeier, 2006; Ringrose et al, 2003; Zeng, Kirk, Gou, Wang, & Ma, 2012). In one study, of 167 potential PREs that Ringrose et al (2003) identified, only 16% of them were PcG binding sites in PcG ChIP genome-wide studies of Drosophila embryos (Schuettengruber et al, 2009).…”

Section: Pres In Drosophilamentioning

confidence: 99%

Polycomb Group Response Elements in Drosophila and Vertebrates

Kassis¹,

Brown²

2013

Advances in Genetics

201

218

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Polycomb group genes (PcG) encode a group of about 16 proteins that were first identified in Drosophila as repressors of homeotic genes. PcG proteins are present in all metazoans and are best characterized as transcriptional repressors. In Drosophila, these proteins are known as epigenetic regulators because they remember, but do not establish, the patterned expression state of homeotic genes throughout development. PcG proteins, in general, are not DNA binding proteins, but act in protein complexes to repress transcription at specific target genes. How are PcG proteins recruited to the DNA? In Drosophila, there are specific regulatory DNA elements called Polycomb group response elements (PREs) that bring PcG protein complexes to the DNA. Drosophila PREs are made up of binding sites for a complex array of DNA binding proteins. Functional PRE assays in transgenes have shown that PREs act in the context of other regulatory DNA and PRE activity is highly dependent on genomic context. Drosophila PREs tend to regulate genes with a complex array of regulatory DNA in a cell or tissue-specific fashion and it is the interplay between regulatory DNA that dictates PRE function. In mammals, PcG proteins are more diverse and there are multiple ways to recruit PcG complexes, including RNA-mediated recruitment. In this review, we discuss evidence for PREs in vertebrates and explore similarities and differences between Drosophila and vertebrate PREs.

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Section: Pres In Drosophilamentioning

confidence: 99%

Polycomb Group Response Elements in Drosophila and Vertebrates

Kassis¹,

Brown²

2013

Advances in Genetics

201

218

View full text Add to dashboard Cite

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“…In Drosophila, Polycomb response elements (PREs)-with a combination of motifs for a number of transcription factors (TFs) such as PHO, GAGA factor (GAF), and zeste-have been implicated in PRC2 recruitment (Ringrose et al 2003;Schuettengruber et al 2009). Although binding of PHO is indeed observed in nearly all Polycomb domains (Schuettengruber et al 2009), methods to predict PREs based on these motifs perform very poorly (Zeng et al 2012). In vertebrates, PRE sequences remain largely elusive.…”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

Principles of nucleation of H3K27 methylation during embryonic development

et al. 2013

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During embryonic development, maintenance of cell identity and lineage commitment requires the Polycomb-group PRC2 complex, which catalyzes histone H3 lysine 27 trimethylation (H3K27me3). However, the developmental origins of this regulation are unknown. Here we show that H3K27me3 enrichment increases from blastula stages onward in embryos of the Western clawed frog (Xenopus tropicalis) within constrained domains strictly defined by sequence. Strikingly, although PRC2 also binds widely to active enhancers, H3K27me3 is only deposited at a small subset of these sites. Using a Support Vector Machine algorithm, these sequences can be predicted accurately on the basis of DNA sequence alone, with a sequence signature conserved between humans, frogs, and fish. These regions correspond to the subset of blastula-stage DNA methylation-free domains that are depleted for activating promoter motifs, and enriched for motifs of developmental factors. These results imply a genetic-default model in which a preexisting absence of DNA methylation is the major determinant of H3K27 methylation when not opposed by transcriptional activation. The sequence and motif signatures reveal the hierarchical and genetically inheritable features of epigenetic cross-talk that impose constraints on Polycomb regulation and guide H3K27 methylation during the exit of pluripotency.

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“…Thus, despite the unambiguous genetic and genomic evidence for PREs, and for the involvement of PHO and DSP1 in their function, the specificity of the process remains difficult to understand based on studies of individual factors or loci. Thus far, any attempts to predict PREs from genomic sequence alone have only been partly successful (Fiedler and Rehmsmeier, 2006;Kassis and Brown, 2013;Ringrose et al, 2003;Zeng et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Cooperativity, Specificity, and Evolutionary Stability of Polycomb Targeting in Drosophila

Schuettengruber¹,

Elkayam²,

Sexton³

et al. 2014

Cell Reports

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Metazoan genomes are partitioned into modular chromosomal domains containing active or repressive chromatin. In flies, Polycomb group (PcG) response elements (PREs) recruit PHO and other DNA-binding factors and act as nucleation sites for the formation of Polycomb repressive domains. The sequence specificity of PREs is not well understood. Here, we use comparative epigenomics and transgenic assays to show that Drosophila domain organization and PRE specification are evolutionarily conserved despite significant cis-element divergence within Polycomb domains, whereas cis-element evolution is strongly correlated with transcription factor binding divergence outside of Polycomb domains. Cooperative interactions of PcG complexes and their recruiting factor PHO stabilize PHO recruitment to low-specificity sequences. Consistently, PHO recruitment to sites within Polycomb domains is stabilized by PRC1. These data suggest that cooperative rather than hierarchical interactions among low-affinity sequences, DNA-binding factors, and the Polycomb machinery are giving rise to specific and strongly conserved 3D structures in Drosophila.

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Genome-wide polycomb target gene prediction in Drosophila melanogaster

Cited by 27 publications

References 104 publications

Polycomb Group Response Elements in Drosophila and Vertebrates

Polycomb Group Response Elements in Drosophila and Vertebrates

Principles of nucleation of H3K27 methylation during embryonic development

Cooperativity, Specificity, and Evolutionary Stability of Polycomb Targeting in Drosophila

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