Dynamic continuity of nuclear and mitotic matrix proteins in the cell cycle

Abstract

The eukaryotic cell nucleus is a membrane-enclosed compartment containing the genome and associated molecules supported by a highly insoluble filamentous network known as the nucleoskeleton or nuclear matrix. The nuclear matrix is believed to play roles in maintaining nuclear architecture and organizing nuclear metabolism. Recently, advances in microscopic techniques and the availability of new molecular probes have made it possible to localize functional domains within the nuclear matrix and demonstrate dynamic interactions between both soluble and insoluble components involved in the control of multiple nuclear transactions. Like the cytoplasm and its skeleton, the nucleoplasm is highly structured and very crowded with an equally complex skeletal framework. In fact, there is growing evidence that the two skeletal systems are functionally contiguous, providing a dynamic cellular matrix connecting the cell surface with the genome. If we impose cell cycle dynamics upon this skeletal organization, it is obvious that the genome and associated nuclear matrix must undergo a major structural transition during mitosis, being disassembled and/or reorganized in late G2 and reassembled again in daughter nuclei. However, recent evidence from our laboratory and elsewhere suggests that much of the nuclear matrix is used to form the mitotic apparatus (MA). Indeed, both facultative and constitutive matrix-associated proteins such as NuMA, CENP-B, CENP-F, and the retinoblastoma protein (Rb) associate within and around the MA. During mitosis, the nuclear matrix proteins may either become inert "passengers" or assume critical functions in partitioning the genome into newly formed G1 nuclei. Therefore, we support the view that the nuclear matrix exists as a dynamic architectural continuum, embracing the genome and maintaining cellular regulation throughout the cell cycle.

Automated local bright feature image analysis of nuclear protein distribution identifies changes in tissue phenotype

“…Several nuclear proteins have been reported to display a specific compartmentalization (e.g., within the nucleolus, nuclear domains, or chromatin), and distribution (e.g., diffuse or aggregated), which change during the cell cycle (3,4), upon a switch between proliferation and growth arrest (5), or after cell differentiation (6)(7)(8)(9). Studies using three-dimensional (3D) culture of breast epithelial cells in the presence of laminin-rich extracellular matrix have revealed that the distribution of certain nuclear proteins depends also on tissue morphogenesis (5,10).…”

Role of Nuclear Matrix in Estrogen Regulated Gene Expression in Human Breast Cancer Cells

“…It has been postulated that the nuclear matrix has a role in the expression of genes by concentrating a subset of transcription factors at specific nuclear sites (Stein et al, 1991;Merriman et al, 1995). Transcription factors associated with the nuclear matrix include ER, HET, GATA-1, YY1, AML-1, Spl, Octl, mutant p53, and Rb (Dworetzky et al, 1992;Isomura et al, 1992;Vassetzky et al, 1993;van Wijnen et al, 1993;Merriman et al, 1995;Guo et al, 1995;Müller et al, 1996;Mancini et al, 1996;Kim et al, 1996;.…”

Mechanogenomic Control of DNA Exposure and Sequestration

“…These observations are consistent with the idea that alterations in higher order chromatin structure and may, in part, be controlled by disulfide-rich nuclear matrix proteins, [15][16][17][18][19][20][21] which orchestrate widespread changes in restriction enzyme site exposure and sequestration. However, these digestion experiments also suggest that the disulfide-rich nuclear matrix cannot be a static or fixed structure, which is consistent with current models of chromatin structure and higher order nuclear organization of gene regulatory machinery in nuclear matrix-associated microenvironments that support combinatorial control of gene expression by dynamic, physiologically responsive targeting and retention mechanisms.…”