Article ID Journal Published Year Pages File Type
2824619 Trends in Genetics 2015 12 Pages PDF
Abstract

Pericentromeric DNA represents a large fraction of the mammalian genome that is usually assembled into heterochromatin. Recent advances have revealed that the composition of pericentromeric heterochromatin is surprisingly dynamic. Indeed, high levels of histone H3 trimethylation on lysine 9 (H3K9me3) and DNA methylation normally characterize the repressive environment of this region. However, in specific tissues and in cancer cells, Polycomb proteins can occupy pericentromeric heterochromatin and act as a molecular sink for transcriptional regulators. Restoring heterochromatin methylation marks could, thus, be an important way to bring back normal gene expression programs in disease. Here, I discuss the potential mechanisms by which Polycomb complexes are recruited to pericentromeric DNA.

TrendsPericentromeric heterochromatin adopts distinct epigenetic signatures upon developmental cues or in pathological conditions such as cancer.H3K9me3 and DNA methylation represent the most common state of this heterochromatin and perturbing this regulation allows for Polycomb group protein recruitment at pericentromeres.Recent work has provided important molecular details on how Polycomb factors are recruited to this locus, and a key requisite is DNA hypomethylation.Understanding how PcG proteins bind to pericentromeric heterochromatin will give insights into how PcG proteins target their genes, and will also help understanding the function of pericentromeres in the control of gene expression.

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Life Sciences Biochemistry, Genetics and Molecular Biology Genetics
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