Nuclear Compartments: An Incomplete Primer to Nuclear Compartments, Bodies, and Genome Organization Relative to Nuclear Architecture

Abstract

This work reviews nuclear compartments, defined broadly to include distinct nuclear structures, bodies, and chromosome domains. It first summarizes original cytological observations before comparing concepts of nuclear compartments emerging from microscopy versus genomic approaches and then introducing new multiplexed imaging approaches that promise in the future to meld both approaches. I discuss how previous models of radial distribution of chromosomes or the binary division of the genome into A and B compartments are now being refined by the recognition of more complex nuclear compartmentalization. The poorly understood question of how these nuclear compartments are established and maintained is then discussed, including through the modern perspective of phase separation, before moving on to address possible functions of nuclear compartments, using the possible role of nuclear speckles in modulating gene expression as an example. Finally, the review concludes with a discussion of future questions for this field.

Arg-tRNA synthetase links inflammatory metabolism to RNA splicing and nuclear trafficking via SRRM2

“…SRRM2 is a nuclear speckle protein and spliceosome component, and RNA transcription splicing have been reported to take place at or in close proximity to nuclear speckles (Belmont, 2021; Chen and Belmont, 2019). A recent model suggested that splice-site selection is regulated by partial immersion of unspliced pre-mRNA at the interface between nuclear speckles and nucleoplasm (Liao and Regev, 2021).…”

True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin

“…Physical maps of nuclear landscapes, supplemented with biochemical information about epigenetic markers and attachment sites of specific macromolecules and functional complexes, have revolutionized our views on nuclear organization. How nuclear compartments are established and maintained, and how they interact functionally, has remained a largely unsolved problem (Belmont, 2021;Misteli, 2020).…”

Phase Separation and Correlated Motions in Motorized Genome

“…Euchromatin and heterochromatin are known to exhibit distinct chemical modifications [27][28][29][30] and interact with different regulatory proteins 28,29 and nuclear bodies. 9,[31][32][33] The chemical modifications themselves could drive chromatin demixing by altering nucleosome interactions. For example, acetylation could neutralize the positive charges on histone tails to weaken their binding with DNA, [34][35][36][37] while methylation may lead to under-twisted DNA that strengthens its interactions with histones.…”