A proposed unified interphase nucleus chromosome structure: Preliminary preponderance of evidence

Abstract

Cryoelectron tomography of the cell nucleus using scanning transmission electron microscopy and deconvolution processing technology has highlighted a large-scale, 100- to 300-nm interphase chromosome structure, which is present throughout the nucleus. This study further documents and analyzes these chromosome structures. The paper is divided into four parts: 1) evidence (preliminary) for a unified interphase chromosome structure; 2) a proposed unified interphase chromosome architecture; 3) organization as chromosome territories (e.g., fitting the 46 human chromosomes into a 10-μm-diameter nucleus); and 4) structure unification into a polytene chromosome architecture and lampbrush chromosomes. Finally, the paper concludes with a living light microscopy cell study showing that the G1 nucleus contains very similar structures throughout. The main finding is that this chromosome structure appears to coil the 11-nm nucleosome fiber into a defined hollow structure, analogous to a Slinky helical spring [ https://en.wikipedia.org/wiki/Slinky ; motif used in Bowerman et al. , eLife 10, e65587 (2021)]. This Slinky architecture can be used to build chromosome territories, extended to the polytene chromosome structure, as well as to the structure of lampbrush chromosomes.

Perspective Article: Space-time dynamics of genome replication studied with super-resolved microscopy

“…For a comprehensive understanding of genome replication, it is necessary to understand the space-dynamics of an interphase chromatin organization that allows the apparently instantaneous formation of mitotic chromosomes with two sister chromatids at the onset of prophase required for the faithful separation of chromatids during anaphase [64] and the rapid reformation of functional 4D nucleomes in daughter cells. The spatial separation of daughter CDs arranged along the two sister chromatids formed in each CT during S-phase likely starts as soon as such a pair is formed.…”

Helical Coiled Nucleosome Chromosome Architectures during Cell Cycle Progression

“…We extend the analysis of the coiled chromosome structures described in our recent studies (20,22). The Slinky structures, interphase S, prophase S' and mitotic S'', are now built as a time series showing these structures coiling (Figure 1).…”

“…Detailed 3-Dimensional optical microscopy will also greatly help prophase S' and mitotic S'' structure determination. In this regard, the polarization microscopy/birefringence optical studies of nuclei, suggesting ordered structures, may need to be re-examined; the nuclear substructure, never interpreted or understood (66), is reminiscent of the interphase S architecture described in (20)…”

“…These coils resulted from a partial specific uncoiling of the mitotic chromosome in telophase (see panel C), and are called Primordial Coils to emphasize their organizational relationship in the cell cycle; these coils were the basis of chromosome territories described in Figure 4. Below the level of the Primordial Coils is the interphase chromosome structure, helically coiled structure of the nucleosome 11nm fiber, interphase S, extensively described in (20) and Figure 1.…”

Lampbrush chromosome studies in the post‐genomic era

“…Lampbrush chromosomes serve as a fascinating model for exploration into fundamental aspects of chromosome biology, such as mechanisms and dynamics of transcription, co-transcriptional stages of RNA processing, formation of loci-associated nuclear domains [6,7] It has been proposed that lampbrush chromosome structure with extended transcription loops bounded by regions of compact chromatin can integrate into the general interphase chromosome architecture. [8] Examining the organization of transcription units and nascent RNA processing in the lateral loops of lampbrush chromosomes, which strongly resemble the transcription loops in interphase chromatin, [3] can provide valuable information on the regulation and dynamics of transcription of eukaryotic genes. However, until recently, the information on the spectrum of transcribed sequences as well as genomic context of individual chromomeres was mainly confined to tandemly repetitive elements.…”