PMC

Bivalent associations where a specific nucleolar bivalent is forming part, in spermatocytes 2n = 40 and nucleolar derivatives, in spermatocytes 2n = 24 or 2n = 32. (a) bivalent 12; (a′) bivalent Rb 10.12; (a″) trivalent 10:10.12:12; (b) bivalent 15; (b′) bivalent Rb 5.15; (b″) trivalent 5:5.15:15; (c) bivalent 16; (c′) bivalent Rb 16.17; (c″) trivalent 16:16.17:17. By immunofluorescence the SCs of the bivalents (light blue) and the fibrillarin of the nucleoli (red) are shown. The specific nucleolar bivalents/trivalents were identified by FISH with a probe against the chromatin of the respective nucleolar telocentric chromosome (green). The heterochromatin was stained with DAPI (blue). Bar = 10 µm. (a) Bivalent 12 is producing an abundant nucleolus and it is associated through heterochromatin to another bivalent; (b) bivalent 15 is not producing a nucleolus and it is associated through heterochromatin to three other bivalents one of them a nucleolar one that has a nucleolus associated; (c) bivalent 16 is producing a nucleolus and is associated through heterochromatin to three other bivalents; (a′) bivalent 10.12 is producing a small nucleolus and it is associated through heterochromatin to another metacentric bivalent; (b′) bivalent 5.15 is producing a medium nucleolus and it is associated through heterochromatin to three metacentric bivalents; (c′) bivalent 16.17 is not producing a nucleolus and it is associated through heterochromatin to three metacentric bivalents; (a″); (b″) and (c″) all show one nucleolar trivalent with a nucleolus and not associated with other bivalents at all.

Schematic of the chromatin structure and the nucleus. DNA wraps around an octamer of histones (two H2A, two H2B, two H3, and two H4) to form a nucleosome and the chromatin fiber. The chromatin fiber is folded to organize into complex structures of chromatin domains. LAD, lamina-associated domain. TAD, topologically associated domain, i.e., chromatin domain, which associates with each other to create chromatin compartments. Chromosome territory, the DNA of a chromosome. During metaphase of cell division, the chromatins are condensed into higher orders of structures, chromosomes, which are detectable by conventional light microscopy. For brevity, other structures such as nucleolus and Cajal body and molecules in the nucleus are not illustrated.

A summary of similarities and associations among sex body, inactive X chromosome (Barr body), heterochromatin, and nucleolus. Sex body, Barr body, and heterochromatin are all physically associated with the nucleolus. While heterochromatin and nucleolus are confirmed to be driven by phase separation, sex body and Barr body are hypothesized to be formed by LLPS. In addition, sex body, Barr body, and heterochromatin all present inactive chromatin state, dramatic chromatin modifications, chromosome reorganizations. These similarities and associations raise the possibility that sex body is formed by LLPS.

Some key research areas towards a unified model of chromatin hubs. (a) Identification of chromatin domains able to form chromatin hubs. In the figure, hypothetical TADs, LADs, NADs, and PADs are identified. (b) Nuclear body/chromatin hub biogenesis. In the figure, we show a model where liquid–liquid phase separation occurs near NADs forming small nucleoli, which then coalesce, generating a large nucleolus with an associated chromatin hub. (c) Common and distinct biological pathways in nuclear bodies and their effect on both organelle identity and chromatin binding. In the figure, nuclear speckles are shown to share different proteins with other nuclear bodies. (d) Chromatin domain potential for joining different repressive or active compartments and oscillating between them. In the figure, a hypothetical chromatin domain shows the potential to bind to four different nuclear structures.