Polycomb and Trithorax Group Genes in <i>Drosophila</i>

Kassis, Judith A.; Kennison, James A.; Tamkun, John W.

doi:10.1534/genetics.115.185116

Cited by 193 publications

(209 citation statements)

References 308 publications

(384 reference statements)

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“…E(Pc) mutants did not have homeotic phenotypes as did the Polycomb group mutants, which have defects in silencing HOX gene expression (Kassis et al 2017). Instead E(Pc) mutants acted as dominant enhancers of Polycomb group mutants in adult flies, indicating unique underlying genetic interactions; E(Pc) −/− flies, however, are themselves embryonic lethal (Cheng et al 1994; Sato et al 1983; Soto et al 1995).…”

Section: Enhancer Of Polycomb Is Broadly Conservedmentioning

confidence: 99%

Critical genomic regulation mediated by Enhancer of Polycomb

Searle

Pillus

2017

Curr Genet

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Enhancer of Polycomb (EPC) was first identified for its contributions to development in Drosophila and was soon-thereafter purified as a subunit of the NuA4/TIP60 acetyltransferase complex. Since then, EPC has often been left in the shadows as an essential, yet non-catalytic subunit of NuA4/TIP60; however, its deep conservation and disease association make clear that it warrants additional attention. In fact, recent studies in yeast demonstrated that its Enhancer of Polycomb, Epl1, was just as important for gene expression and acetylation as is the catalytic subunit of NuA4. Despite its conservation, studies of EPC have often remained siloed between organisms. Here, our goal is to provide a cohesive view of the current state of the EPC literature as it stands among the major model organisms in which it has been studied. EPC is involved in multiple processes, beginning with its cardinal role in regulating global and targeted histone acetylation. EPC also frequently serves as an important interaction partner in these basic cellular functions, as well as in multicellular development, such as in hematopoiesis and skeletal muscle differentiation, and in human disease. Taken together, a unifying theme from these studies highlights EPC as a critical genomic regulator.

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Section: Enhancer Of Polycomb Is Broadly Conservedmentioning

confidence: 99%

Critical genomic regulation mediated by Enhancer of Polycomb

Searle

Pillus

2017

Curr Genet

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“…Most of those tested did not have an obvious effect ( Figure 8A). However, inhibition of the Polycomb group gene extra sex combs (esc), which encodes a component of the PRC2 (reviewed by (Kassis et al, 2017), specifically during the regeneration period using DUAL Control consistently improved regeneration, even in discs ablated in early L3 ( Figure 8B). We used the weaker PDM2-driven version of DUAL Control for these experiments to avoid the pleotropic effects and lethality associated with strong or widespread knockdown of epigenetic regulators.…”

Section: Using Dual Control To Screen For Chromatin Modifiers That Inmentioning

confidence: 99%

Regenerative capacity inDrosophilaimaginal discs is controlled by damage-responsive, maturity-silenced enhancers

Harris

Stinchfield

Nystrom

et al. 2019

Preprint

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Like tissues of many organisms, Drosophila imaginal discs lose the ability to regenerate as they mature. This loss of regenerative capacity coincides with reduced damage-responsive expression of multiple genes needed for regeneration. Our previous work showed that two such genes, wg and Wnt6, are regulated by a single damage-responsive enhancer, which becomes progressively inactivated via Polycomb-mediated silencing as discs mature. Here we explore the generality of this mechanism, and identify numerous damage-responsive, maturity-silenced (DRMS) enhancers, some near genes known to be required for regeneration such as Mmp1, as well as near genes that we now show function in regeneration. Using a novel GAL4-independent tissue ablation system we characterize two DRMS-associated genes, apontic (apt), which curtails regeneration and CG9752/asperous (aspr), which promotes it. This mechanism of suppressing regeneration by silencing damage-responsive enhancers at multiple loci can be partially overcome by reducing activity of the chromatin regulator extra sex combs (esc).

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“…There are several major epigenetic regulators that contribute to maintaining a regulatory state over many cell divisions. Among them, Polycomb group (PcG) and Trithorax group (TrxG) proteins act epigenetically in functional opposition to maintain gene expression patterns as cells differentiate during embryogenesis: PcGs maintain gene silencing, whereas TrxGs act as anti-repressors to counteract PcG function (10)(11)(12). PcG proteins contribute to the formation of a specific type of repressive chromatin structure called a Polycomb domain which, for example, represses the expression of nonfunctional Hox genes during segmentation of the Drosophila embryo (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide Prediction of Potential Polycomb Response Elements and their Functions

Khabiri

2019

Preprint

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The Polycomb-group proteins (PcG) and Trithorax-group proteins (TrxG) are two major epigenetic regulators important for proper differentiation during development (1,2). In Drosophila melanogaster (D. melanogaster), Polycomb response elements (PREs) are short segments of DNA with a high density of binding sites for transcription factors (TFs) that recruit PcG and TrxG proteins to chromatin. Each PRE has a different number of binding sites for PcG and TrxG, and these binding sites have different topological organizations. It is thus difficult to find general rules to discover the locations of PREs over the entire genome. We have developed a framework to predict the locations and roles of potential PRE regions over the entire D. melanogaster genome using machine learning algorithms. Using a combination of motif-based and simple sequence-based features, we were able to train a random forest (RF) model with very high performance in predicting active PRE regions. This model could distinguish potential PRE regions from non-PRE regions (precision and recall ~0.92 upon cross-validation). In the process, the model suggests that previously unrecognized TFs might contribute to PcG/TrxG recruitment at the PRE locations, as the presence of binding sites for those factors is strongly informative of active PREs. A secondary regression model provides information on features that further differentiate PREs into functional subclasses. Our findings provide both new predictions of 7887 potential PREs in the D. melanogaster genome, and new mechanistic insight into the set of DNA-associated proteins that may contribute to PcG recruitment and/or activity. Author summaryDuring the development of multicellular organisms, the pattern of gene expression for every cell type must be established and then inherited through cell division. DNA cis-regulatory elements called Polycomb response elements (PREs) are major drivers of the spatio-temporal regulation of many genes during development. Recently, it has been reported that, depending on the cell type and condition, these elements could have dual functionality: a PRE can act as a silencing element in one cell type and an enhancer in others. Integrating all binding information of characterized TFs with DNA sequence features allowed us to construct a highly informative machine learning model to predict and classify PRE locations. Applying our model to Drosophila both allowed us to identify many new putative PREs (15-16 times the number currently known from experimental studies) and provides insight into the specific DNA-binding proteins that may additionally contribute to PRE function.

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Polycomb and Trithorax Group Genes in Drosophila

Cited by 193 publications

References 308 publications

Critical genomic regulation mediated by Enhancer of Polycomb

Critical genomic regulation mediated by Enhancer of Polycomb

Regenerative capacity inDrosophilaimaginal discs is controlled by damage-responsive, maturity-silenced enhancers

Genome-wide Prediction of Potential Polycomb Response Elements and their Functions

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