Mitotic chromosomes

Spanos

et al. 2021

Preprint

Self Cite

We have used a combination of chemical genetics, chromatin proteomics and imaging to map the earliest chromatin transactions during vertebrate cell entry into mitosis. Chicken DT40 CDK1as cells undergo synchronous mitotic entry within 15 minutes following release from a 1NM-PP1-induced arrest in late G2. In addition to changes in chromatin association with nuclear pores and the nuclear envelope, earliest prophase is dominated by changes in the association of ribonucleoproteins with chromatin, particularly in the nucleolus, where pre-rRNA processing factors leave chromatin significantly before RNA polymerase I. Nuclear envelope barrier function is lost early in prophase and cytoplasmic proteins begin to accumulate on the chromatin. As a result, outer kinetochore assembly appears complete by nuclear envelope breakdown (NEBD). Most interphase chromatin proteins remain associated with chromatin until NEBD, after which their levels drop sharply. An interactive proteomic map of chromatin transactions during mitotic entry is available as a resource at https://mitoChEP.bio.ed.ac.uk.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mapping the invisible chromatin transactions of prophase chromosome remodelling

Spanos

et al. 2021

Preprint

Self Cite

“…One of the most remarkable visual events in cell biology is chromosome condensation, which takes place when cells transit from G2 into prophase and metaphase (M phase). In higher eukaryotes, chromosomes are condensed over a central scaffold formed by topoisomerase II alpha, condensin I and condensin II 1 . Condensation requires the reorganization of the chromatin fiber into nested loops [1][2][3] , so that chromosomes progressively shorten their length while becoming wider.…”

Section: Introductionmentioning

confidence: 99%

“…In higher eukaryotes, chromosomes are condensed over a central scaffold formed by topoisomerase II alpha, condensin I and condensin II 1 . Condensation requires the reorganization of the chromatin fiber into nested loops [1][2][3] , so that chromosomes progressively shorten their length while becoming wider. The formation and expansion of these loops continues until chromosomes acquire their characteristic rod-like appearance by late metaphase.…”

Section: Introductionmentioning

confidence: 99%

Nuclear envelope reshaping around the vacuole determines the morphology of the ribosomal DNA

Matos-Perdomo

Santana-Sosa

Ayra-Plasencia

et al. 2021

Preprint

The ribosomal DNA array (rDNA) of Saccharomyces cerevisiae has served as a model to address chromosome organization. In cells arrested before anaphase (mid-M), the rDNA acquires a highly structured chromosomal organization referred to as the rDNA loop, whose length can double the cell diameter. Previous works established that complexes such as condensin and cohesin are essential to attain this structure. Here, we report that the rDNA loop adopts distinct morphologies that arise as spatial adaptations to changes in the nuclear morphology triggered during the mid-M arrests. Interestingly, the formation of the rDNA loop results in the appearance of a space under the loop (SUL) which is devoid of any nuclear component yet colocalizes with the vacuole. We finally show that the formation and maintenance of the rDNA loop and the SUL require TORC1 and membrane synthesis. We propose that the rDNA-associated nuclear envelope (NE) reshapes into a loop to accommodate the vacuole, with the nucleus becoming bilobed.

“…Within unreplicated chromosomes, a single continuous DNA molecule is tightly packaged into higher order structures. Nucleosomes form the chromatin fibre which are proposed to fold into consecutive chromatin loops [2][3][4] that are assembled into distinct chromosomal domains (topologically associating domains (TADs) in animals 5,6 and TAD-like domain structures in plants 7,8 . The importance of chromatin packaging lays in its impact on DNA accessibility that consequently affects the fundamental processes of transcription, replication, and recombination.…”

Section: Introductionmentioning

confidence: 99%

A Multigraph model of the 3D genome

Makai

Cseh

Sepsi

et al. 2021

Preprint

Spatial organisation of the genome has a fundamental effect on its biological functions. Chromatin-chromatin interactions and 3D spatial structures are involved in transcriptional regulation and have a decisive role in DNA replication and repair. To understand how individual genes and their regulatory elements function within the larger genomic context, and how the genome reacts as a whole to environmental stimuli, the linear sequence information needs to be interpreted in 3-dimensional space. While recent advances in chromatin conformation capture technologies including Hi-C, considerably advanced our understanding of the genomes, defining the DNA, as it is organized in the cell nucleus is still a challenging task. 3D genome modelling needs to reflect the DNA as a flexible polymer, which can wind up to the fraction of its total length and greatly unwind and stretch to implement a multitude of functions. Here we propose a novel approach to model genomes as a multigraph based on Hi-C contact data. Multigraph-based 3D genome modelling of barley and rice revealed the well-known Rabl and Rosetta chromatin organizations, respectively, as well as other higher order structures. Our results shows that the well-established toolset of Graph theory is highly valuable in modelling large genomes in 3D.