Order and Disorder in the Nucleus

Abstract

Fluorescence in situ hybridization combined with three-dimensional microscopy has shown that chromosomes are not randomly strewn throughout the nucleus but are in fact fairly well organized, with different loci reproducibly found in different regions of the nucleus. At the same time, increasingly sophisticated methods to track and analyze the movements of specific chromosomal loci in vivo using four-dimensional microscopy have revealed that chromatin undergoes extensive Brownian motion. However, the diffusion of interphase chromatin is constrained, implying that chromosomes are physically anchored within the nucleus. This constraint on diffusion is the result of interactions between chromatin and structural elements within the nucleus, such as nuclear pores or the nuclear lamina. The combination of defined positioning with constrained diffusion has a strong impact on interactions between chromosomal loci, and appears to explain the tendency of certain chromosome rearrangements to occur during the development of cancer.

Histone Acetyltransferase hALP and Nuclear Membrane Protein hsSUN1 Function in De-condensation of Mitotic Chromosomes

“…Chromosomes are structurally organized and occupy discrete nuclear territories (43). The nuclear envelope provides a scaffold for anchoring chromatin and for maintaining nuclear integrity (32,44).…”

“…The nuclear envelope provides a scaffold for anchoring chromatin and for maintaining nuclear integrity (32,44). Nuclear envelope and associated proteins such as nuclear lamina, NPC, LAP2, LBR, and emerin directly or indirectly interact with chromatin to regulate DNA replication and transcription (27,43,45). A pivotal event in the mammalian cell cycle is nuclear membrane dissolution as a cell enters mitosis.…”

Radiation-induced DNA damage and delayed induced genomic instability

“…Ionizing radiation causes large deletions or abnormal positioning of telomeres, which give rise to PUCRs, and they are supposed to alter the chromatin architecture within the nucleus. Furthermore, recent studies identify nuclear matrixattachment regions (MARs) along the entire length of chromosomes Marshall, 2002;Parada and Misteli, 2002). Since MARs and telomeres might act as anchoring sites and thereby chromosomes are restrained from movement, loss of these sites untethers chromosomes from their confined domains.…”

Non-random positioning of chromosomes in human sperm nuclei

“…It is tempting to speculate that activities of genes on specific chromosomes are influenced dynamically by their chromosomal and nuclear position (Blobel 1985, HeslopHarrison 1996, Croft et al 1999. Indeed, spatial arrangement of chromosomes both during prometaphase/metaphase and in interphase is apparently non-random , Parada & Misteli 2002, Marshall 2002, Gasser 2002). An ordered relative position of chromosomes during prometaphase/metaphase has been observed both in plant (Ashley 1979, Oud et al 1989) and in animal (Leitch et al 1994, Nagele et al 1995 cells.…”