Abstract
Epigenome modifications are established early in development and differentiation and generate distinct levels of chromatin complexity. The specific position of chromosomes and the compaction state of chromatin are both typical features that make it possible to distinguish between repressive and permissive environment for gene expression. In this review we describe the distinct levels of epigenome structures, emphasizing the role of nuclear architecture in the control of gene expression. Recent novel insights have increasingly demonstrated that the nuclear environment can influence nuclear processes such as gene expression and DNA repair. These findings have revealed a further important aspect of the chromatin modifications, suggesting that a proper crosstalk between chromatin and nuclear components, such as lamins or nuclear pores, is required to ensure the correct functioning of the nucleus and that this assumes a crucial role in many pathologies and diseases. Knowledge regarding the molecular mechanisms behind most of these developmental and disease-related defects remains incomplete; the influence of the nuclear architecture on chromatin function may provide a new perspective for understanding these phenotypes.
Highlights
Constitutive heterochromatin is marked with H3K9me3 catalyzed by Suv39H [21], which in turn stimulates the recruitment of Heterochromatin Protein 1(HP1) [22], so contributing to form a closed chromatin structure normally associated with a repressive transcriptional state
PcG proteins leave lineage specific muscle promoters and bind genes important for stemness maintenance [46]. This dynamics has been extensively shown in muscle differentiation: in muscle stem cells muscle specific genes are maintained repressed by PcG proteins; at the onset of muscle differentiation PcG proteins are displaced from muscle gene and are relocalized at stemness genes, such as Pax7, ensuring the correct timing of the muscle differentiation [47,48,49,50,51]
As summarized in this review, the organization of the nucleus and the compartmentalization of chromatin are fundamental for gene expression regulation and, as recent studies show, can both influence specific cellular processes such as DNA repair
Summary
DNA is packaged inside the nucleus through its ordered and repetitive aggregation with histones and is bound by several proteins and RNA molecules: the overall complex of nucleic acids and their associated proteins is known as “chromatin”. The first level of chromatin organization is the nucleosome: four histone proteins; H2A, H2B, H3, H4 surrounded by DNA [1]. Each nucleosome is separated from the one by a DNA linker, variable in length, which is associated to histone H1 and or its variants [2,3]. These DNA-histones complexes fold in 30 nm fibers. This process is driven in part by the histone H1, which regulates the intranuclear electrostatic balance and by nucleosome repeats which ensure the stabilization of chromatin fibers [4,5,6]. The facultative heterochromatin is a repressive environment able to rapidly shift between activated and repressed state through the crosstalk with epigenetic regulators that lead to a chromatin reorganization [8]
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