Histones and histone modifications in perinuclear chromatin anchoring: from yeast to man

Abstract

It is striking that within a eukaryotic nucleus, the genome can assume specific spatiotemporal distributions that correlate with the cell's functional states. Cell identity itself is determined by distinct sets of genes that are expressed at a given time. On the level of the individual gene, there is a strong correlation between transcriptional activity and associated histone modifications. Histone modifications act by influencing the recruitment of non‐histone proteins and by determining the level of chromatin compaction, transcription factor binding, and transcription elongation. Accumulating evidence also shows that the subnuclear position of a gene or domain correlates with its expression status. Thus, the question arises whether this spatial organization results from or determines a gene's chromatin status. Although the association of a promoter with the inner nuclear membrane (INM) is neither necessary nor sufficient for repression, the perinuclear sequestration of heterochromatin is nonetheless conserved from yeast to man. How does subnuclear localization influence gene expression? Recent work argues that the common denominator between genome organization and gene expression is the modification of histones and in some cases of histone variants. This provides an important link between local chromatin structure and long‐range genome organization in interphase cells. In this review, we will evaluate how histones contribute to the latter, and discuss how this might help to regulate genes crucial for cell differentiation.

Nonrandom domain organization of the Arabidopsis genome at the nuclear periphery

“…An intriguing question is which factors are involved in specifically tethering chromatin to the plant nuclear periphery. In animals, lamins and lamin-associated proteins have been identified as key factors involved in these events (for review, see Harr et al 2016). Unfortunately, to identify the counterparts in plants, a strategy based on a protein-sequence similarity search might be of little use compared to forward genetics approaches, because plants lack orthologs of lamins and most lamin-associated proteins (Ciska and Moreno Díaz de la Espina 2014).…”

On TADs and LADs: Spatial Control Over Gene Expression

“…For an integrated array, H3K9me1 and H3K9me2 were sufficient for peripheral sequestration[ 1 4 5 _ T D $ D I F F ] , while H3K9me3 was necessary for full repression[ 1 4 6 _ T D $ D I F F ] of the array-borne reporter [43]. A similar dependence on H3K9 methylation was demonstrated for LAD anchoring in mammals (reviewed in [47]). Recently, a novel C. elegans chromodomain protein that specifically recognizes methylated H3K9 (CEC-4), was shown to mediate the perinuclear sequestration of heterochromatic arrays and of chromosome arms enriched for H3K9 methylation [48].…”

Chromatin organization at the nuclear periphery as revealed by image analysis of structured illumination microscopy data

“…Depending on its transcriptional status, chromatin has been shown to associate with different parts of the nucleus Cavalli and Misteli, 2013). Among these, the nuclear envelope (NE) serves as a principal region for chromatin compartmentalization to which both active and inactive genes are targeted (Egecioglu and Brickner, 2011;Harr et al, 2016). In recent years, a substantial effort has been undertaken to understand the mechanism of chromatin targeting to the NE, including its causes and consequences.…”

“…In general, the modifications H3K9me3, H2K9me, H3K27me2 and H3K27me3, as well as the recently described H3K23me2 (Vandamme et al, 2015), are associated with transcriptional silencing and formation of heterochromatin (Bannister and Kouzarides, 2011). The modifications associated with transcription activation are H3K4me3, H4K2me, H3K9Ac, H3K36me3 and H4K5Ac (Harr et al, 2016). The changes in histone modifications are directed by groups of enzymes responsible for addition or removal of the respective modification.…”

“…The changes in histone modifications are directed by groups of enzymes responsible for addition or removal of the respective modification. Methyl groups are actively removed by histone demethylases, whereas removal of acetyl group is catalyzed by histone deacetylases (reviewed in Harr et al, 2016). There are two distinct families of mammalian histone demethylases with a growing number of their members often showing a functional overlap.…”