Abstract
Chromatin regulators of the Polycomb group of genes are well-known by their activities as transcriptional repressors. Characteristically, their presence at genomic sites occurs with specific histone modifications and sometimes high-order chromatin structures correlated with silencing of genes involved in cell differentiation. However, evidence gathered in recent years, on flies and mammals, shows that in addition to these sites, Polycomb products bind to a large number of active regulatory regions. Occupied sites include promoters and also intergenic regions, containing enhancers and super-enhancers. Contrasting with occupancies at repressed targets, characteristic histone modifications are low or undetectable. Functions on active targets are dual, restraining gene expression at some targets while promoting activity at others. Our aim here is to summarize the evidence available and discuss the convenience of broadening the scope of research to include Polycomb functions on active targets.
Highlights
The genetic information encoded in eukaryotic DNA is managed through the intertwined actions of a large collection of transcription factors and chromatin regulators
The following is the overview of the biochemistry and functionality of the Polycomb system, most of which derives from studies aimed at understanding its role as chromatin regulators in gene repression
Evidence for the activity of Polycomb proteins modulating the expression of active targets is incontrovertible
Summary
The genetic information encoded in eukaryotic DNA is managed through the intertwined actions of a large collection of transcription factors and chromatin regulators. The modified chromatin, the epigenome, resulting from histone modifications, location and mobility of nucleosomes, or DNA methylation include marks that sometimes can be inherited throughout cell divisions As a whole, these modifications depict cell type-specific epigenomic landscapes with predictive properties about the presence and activity of DNA elements essential in transcription regulation, such as enhancers and promoters. The interest on the Polycomb system was significantly encouraged by the key roles in differentiation of stem and oligopotent cells and by their involvement in malignant transformation processes [15,16] Our reference to their functions as transcriptional repressors will be only in passing, to provide some background on the best-known activities of components. The relevance of recent genetic analysis in flies and mice, showing active Polycomb targets as part of tumor suppressor functions and of differentiation programs, led us to believe that this aspect of Polycomb activity merits further work
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