4D Chromatin dynamics in cycling cells: Theodor Boveri's hypotheses revisited

Abstract

This live cell study of chromatin dynamics in four dimensions (space and time) in cycling human cells provides direct evidence for three hypotheses first proposed by Theodor Boveri in seminal studies of fixed blastomeres from Parascaris equorum embryos: (I) Chromosome territory (CT) arrangements are stably maintained during interphase. (II) Chromosome proximity patterns change profoundly during prometaphase. (III) Similar CT proximity patterns in pairs of daughter nuclei reflect symmetrical chromosomal movements during anaphase and telophase, but differ substantially from the arrangement in mother cell nucleus. Hypothesis I could be confirmed for the majority of interphase cells. A minority, however, showed complex, rotational movements of CT assemblies with large-scale changes of CT proximity patterns, while radial nuclear arrangements were maintained. A new model of chromatin dynamics is proposed. It suggests that long-range DNA-DNA interactions in cell nuclei may depend on a combination of rotational CT movements and locally constrained chromatin movements.

Topologically associated domains enriched for lineage-specific genes reveal expression-dependent nuclear topologies during myogenesis

“…During mitosis, the physical constraints of chromosome movement are mitigated as chromosomes condense and the nuclear envelope breaks down. Therefore, it has been hypothesized that mitosis is an ideal time for lineage-specific changes in nuclear organization to occur (48). Unfortunately, the tight coupling of cell division and differentiation made this an untestable hypothesis before the present study.…”

“…How lineage-specific genome topologies emerge is largely not understood. Although it has been observed that chromatin organization in cycling cells maintains a defined organization from interphase through mitosis and to daughter nuclei, this pattern has not been reproducibly demonstrated (35,36,48). Moreover, analyzing the role of the cell cycle in establishing a new nuclear topology during cellular development has remained an intractable problem owing to the tight coupling of proliferation and differentiation.…”

To see an interphase chromosome or: How a disease can be associated with specific nuclear genome organization

“…(reviewed in [13]). Alternatively, current approaches towards studying DNA-based structure of chromosomes can depict locus positioning in four dimensions (space and time), which is relevant not only to basic principles of interphase genome organization, but also to chromosome arrangement in cancer cells [14]. Still, one has to operate with data on arrangement of specific chromosomal loci or ambiguous chromosome territories without an integral view of the whole chromosome at molecular resolution.…”

“…Since the introduction of interphase molecular cytogenetics a significant effort has been made to provide comprehensive information about the meaning of nuclear genome (chromosome) organization [1][2][3][13][14][15]. As a result, interphase chromosome architecture was demonstrated to be involved in critical nuclear processes, which are relevant to cellular homeostasis in health and disease (Box 1).…”

“…Spatiotemporal interphase chromosome organization is highly dynamic [14] and is able to be exogenously manipulated [24,25]. Considering that exogenous influences changing interphase chromosome architecture are far from being completely determined [25], one can already speculate on possible applications of manipulating nuclear structure.…”