The 4D nucleome: Evidence for a dynamic nuclear landscape based on co‐aligned active and inactive nuclear compartments

Abstract

a b s t r a c tRecent methodological advancements in microscopy and DNA sequencing-based methods provide unprecedented new insights into the spatio-temporal relationships between chromatin and nuclear machineries. We discuss a model of the underlying functional nuclear organization derived mostly from electron and super-resolved fluorescence microscopy studies. It is based on two spatially co-aligned, active and inactive nuclear compartments (ANC and INC). The INC comprises the compact, transcriptionally inactive core of chromatin domain clusters (CDCs). The ANC is formed by the transcriptionally active periphery of CDCs, called the perichromatin region (PR), and the interchromatin compartment (IC). The IC is connected to nuclear pores and serves nuclear import and export functions. The ANC is the major site of RNA synthesis. It is highly enriched in epigenetic marks for transcriptionally competent chromatin and RNA Polymerase II. Marks for silent chromatin are enriched in the INC. Multi-scale cross-correlation spectroscopy suggests that nuclear architecture resembles a random obstacle network for diffusing proteins. An increased dwell time of proteins and protein complexes within the ANC may help to limit genome scanning by factors or factor complexes to DNA exposed within the ANC.

Superresolution light microscopy shows nanostructure of carbon ion radiation‐induced DNA double‐strand break repair foci

“…The (53) provides an explanation for the gaps between individual gH2AX subfoci and the H2AX clusters observed with 4Pi microscopy (48).…”

Superresolution imaging reveals structurally distinct periodic patterns of chromatin along pachytene chromosomes

“…This chromatin modulation is done by regulation of DNA binding proteins called histones. The amino acid tails of histones (H2A, H2B, H3, and H4) are subjected to various posttranslational modifications, including acetylation and methylation, which can regulate the compaction of chromatin and modulate gene expression (9). Posttranslational modifications of histones have been shown to contribute to gene expression and recombination during meiosis, but if and how the structure of the pachytene chromosome is regulated by them is still elusive.…”

Nucleoporins redistribute inside the nucleus after cell cycle arrest induced by histone deacetylases inhibition

“…2,3 The functional organization of the nucleus is based on the distribution of chromatin in specific regions of the nucleus, referred to as chromosome territories. [4][5][6][7] The molecular mechanisms underlying this structural arrangement are starting to be understood and 2 models have been proposed: a deterministic model and a self-organization system 7,8,9 . In this regard, large genomic regions associated with the nuclear lamina would be responsible for the functional organization of the nucleus.…”