A role for chromatin topology in imprinted domain regulation

Abstract

Recently, many advancements in genome-wide chromatin topology and nuclear architecture have unveiled the complex and hidden world of the nucleus, where chromatin is organized into discrete neighbourhoods with coordinated gene expression. This includes the active and inactive X chromosomes. Using X chromosome inactivation as a working model, we utilized publicly available datasets together with a literature review to gain insight into topologically associated domains, lamin-associated domains, nucleolar-associating domains, scaffold/matrix attachment regions, and nucleoporin-associated chromatin and their role in regulating monoallelic expression. Furthermore, we comprehensively review for the first time the role of chromatin topology and nuclear architecture in the regulation of genomic imprinting. We propose that chromatin topology and nuclear architecture are important regulatory mechanisms for directing gene expression within imprinted domains. Furthermore, we predict that dynamic changes in chromatin topology and nuclear architecture play roles in tissue-specific imprint domain regulation during early development and differentiation.

The Emergence of Pan-Cancer CIMP and Its Elusive Interpretation

“…Methylation of CpGs in CTCF binding motifs can disrupt genome topology and lead to activation of oncogenes, at least in IDH -mutant gliomas [87]. This is consistent with a role for chromatin topology in the regulation of genomic imprinting [88] and its role in the formation of large hypomethylated regions in CRCs that correspond to nuclear lamina-associated domains [89]. Lamina-associated domains are regions of chromatin located near the periphery of the nucleus and tethered to the intermediate filament lamin.…”

Spatial Genome Organization and Its Emerging Role as a Potential Diagnosis Tool

“…Indeed, for many genes changes in gene expression accompany changes in association with nuclear sub-compartments, including the lamina, nucleolus, transcription factories, heterochromatin, polycomb bodies, NPCs, Cajal bodies and nuclear speckles ( Ahmed et al, 2010 ; Ferrai et al, 2010 ; Bickmore and van Steensel, 2013 ; Khanna et al, 2014 ; Dekker and Misteli, 2015 ; Wang et al, 2016 ). Furthermore, transient co-localization of X chromosomes during the establishment of X inactivation and co-localization of imprinted genes with imprinting control region loci suggest a critical role for spatial genome organization in establishing and maintaining mono-allelic expression in these regions ( Fraser and Bickmore, 2007 ; MacDonald et al, 2016 ). However, radial positioning vs. relative positioning cannot be the full story in explaining the differences between the studies because some genes spatially reposition in the absence of a change in expression.…”