Abstract
In most eukaryotes, constitutive heterochromatin is associated with H3K9me3 and HP1α. The latter has been shown to play a role in heterochromatin formation through liquid–liquid phase separation. However, many other proteins are known to regulate and/or interact with constitutive heterochromatic regions in several species. We postulate that some of these heterochromatic proteins may play a role in the regulation of heterochromatin formation by liquid–liquid phase separation. Indeed, an analysis of the constitutive heterochromatin proteome shows that proteins associated with constitutive heterochromatin are significantly more disordered than a random set or a full nucleome set of proteins. Interestingly, their expression begins low and increases during preimplantation development. These observations suggest that the preimplantation embryo is a useful model to address the potential role for phase separation in heterochromatin formation, anticipating exciting research in the years to come.
Highlights
In eukaryotes, around 145 basepairs of DNA are wrapped around octamers of the four canonical histones H2A, H2B, H3 and H4 to form the nucleosome
Several mass spectrometry studies have been carried out in mammalian cells to better understand the pathways involved in constitutive heterochromatin maintenance and integrity
Most of them focused on the identification of proteins that bind H3K9me3 using peptides or modified nucleosomes pulldowns [39,40,41] or chromatin immunoprecipitation [42,43,44]
Summary
Around 145 basepairs of DNA are wrapped around octamers of the four canonical histones H2A, H2B, H3 and H4 to form the nucleosome. The definition of heterochromatin has broadened to include features such as (i) histone modifications such as histone 3 lysine 9 trimethylation (H3K9me3), H3K27me, DNA methylation and potentially H3K56me3 [3,4]; (ii) a (mostly) transcriptionally silent state; (iii) a late replicating nature; (iv) an electron-dense and condensed state in electron microscopy [5], and more recently (v) a higher resistance to sonication [6]. Heterochromatin can be further broadly divided into constitutive heterochromatin—which is located at centromeric and telomeric regions, as well as at most repeat elements throughout most eukaryotic genomes—and facultative heterochromatin, which harbours the H3K27me mark and often localises to temporally or spatially regulated genes [5]
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