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.
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.
Chromosome territories (CTs) constitute a major feature of nuclear architecture. Recent progress in three‐dimensional (3D) super‐resolution microscopy further supports the following functional model of chromatin organisation: CTs consist of interconnected assemblies of approximately 1 Mb chromatin domains (CDs). These domains are permeated by a 3D channel system, the so‐called interchromatin compartment (IC), which may serve as a preferential compartment for ribonucleic acid (RNA) transport. Wider parts of the IC are nearly deoxyribonucleic acid (DNA) free, expand between CTs and accommodate splicing speckles and nuclear bodies. The interior of CDs contains transcriptionally silent chromatin, whereas their periphery represents a zone of decondensed, transcriptionally competent chromatin. This perichromatin region borders on the network of IC channels and is the site of RNA transcription and DNA replication. During interphase large‐scale movements of CTs are typically absent, although exceptions may exist. In contrast, chromosome neighbourhood arrangements change profoundly during prometaphase resulting in variable CT neighbourhoods arrangements in cycling cells. Key Concepts: Each individual chromosome occupies a distinct region (territory) of the nuclear space. Chromosome territories (CTs) do not occupy fixed positions in the nucleus but show a polarised radial orientation: gene‐dense chromatin is typically located towards the nuclear interior and gene‐poor chromatin at the nuclear periphery. During interphase large‐scale movement of chromatin is not typically observed. Nuclear rotational movements are likely essential for chromatin reorganisation during post‐mitotic differentiation. In cycling cells profound repositioning of chromatin occurs during prometaphase, resulting in new CT neighbourhoods in subsequent daughter nuclei. Recently developed 3D super‐resolution light microscopy provides detailed insight into chromatin ultrastructure and increasing evidence for a highly compartmentalised functional organisation of CTs. We postulate that CTs are built up from interconnected approximately 1 Mb chromatin domains (CD). CDs are permeated by a network of channels, which constitute the interchromatin compartment (IC). The IC is connected to nuclear pores. It accommodates splicing speckles and nuclear bodies and provides a compartment for RNA transport. A zone of decondensed chromatin, called the perichromatin region (PR), is located at the periphery of CDs and lines the IC. It constitutes the site of transcription, splicing, DNA‐replication and possibly also DNA‐repair.
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