These domains are associated with the nuclear matrix (the electron micrograph shown in the center). Immunofluorescence microscopy of the nucleus in situ has revealed the distinct nonoverlapping subnuclear distribution of vital nuclear processes, including DNA replication sites structural parameters of the nucleus (e.g., the nuclear envelope, chromosomes, and chromosomal territories) and Runx transcription factor domains for chromatin organization and transcriptional control of tissue-specific genes, as well as RNA synthesis and processing, involving, for example, transcription sites, SC35 domains, Cajal bodies, and nucleoli. The nuclear architecture is functionally linked to the organization and sorting of regulatory information. More direct evidence for functional linkages between nuclear architecture and transcriptional control was provided by demonstrations that cell growth and phenotypic regulatory factors are nuclear matrix associated and by modifications in the partitioning of transcription factors between the nuclear matrix and the nonmatrix nuclear fraction when changes in gene expression occur (reviewed in Stein et al., 2003 Zaidi et al., 2007).įigure 4. Additional evidence for participation of the nuclear matrix in gene expression came from reports of qualitative and quantitative changes in the representation of nuclear matrix proteins during the differentiation of normal diploid cells and in tumor cells associated with a spectrum of cancers. Regulatory functions of the nuclear matrix include but are by no means restricted to DNA replication ( Berezney and Coffey, 1975), gene location ( Zeng et al., 1997), imposition of physical constraints on chromatin structure that support formation of loop domains, concentration and targeting of transcription factors ( Cai et al., 2006 Dobreva et al., 2006 van Wijnen et al., 1993), RNA processing and transport of gene transcripts ( Blencowe et al., 1994), and post-translational modifications of chromosomal proteins, as well as imprinting and modifications of chromatin structure ( Davie, 1997 Drobic et al., 2006). 4 Bidwell et al., 1994 Dworetzky et al., 1990). The anastomosing network of fibers and filaments that constitute the nuclear matrix supports the structural properties of the nucleus as a cellular organelle and accommodates modifications in gene expression associated with proliferation, differentiation, and changes necessary to sustain phenotypic requirements in specialized cells ( Fig. Actin and an actin-binding protein, tropomyosin, usually associated in a range of cytoplasmic structures, were shown to be associated with the chromosome scaffold in interphase and metaphase chromosomes and function in combination to aid in chromosome compaction. The kinetochore region that anchors the microtubules during spindle formation is also thought to be a part of the scaffolding network. Licensing Factor Model-1 (LFM-1) was found to distribute along the axis and the external surface of the chromatids and is thought to play a role in cell cycle-dependent events. More recently, other components of the chromosome scaffold have been identified. The fluorescently labeled scaffolds appear helically coiled, and the coiling of sister chromatid scaffolds displays a mirror symmetry. SMC2 has been localized to the center of the long axis of the chromatid arms of mitotic metaphase chromosomes by immunofluorescence and has been shown to be very loosely associated with interphase nuclei. ScII, another prominent member of the mitotic chromosome scaffold, is a structural maintenance of chromosomes (SMCs)-type protein, which is now also called SMC2. The first and major part of the chromosome scaffold protein network to be conclusively identified was ScI, identical to topoisomerase II (topo II), which was found to be concentrated in the axial region of the expanded mitotic chromosomes but absent in the loop domains. Two major scaffold proteins (Sc proteins) have been identified, ScI and ScII. The composition of the chromosome scaffold differs based on the species and the developmental stage of the organism, but is predominantly comprised of nonhistone proteins in low abundance (5–10%) forming a structural framework that defines the shape of the chromosome. Sridharan, in Brenner's Encyclopedia of Genetics (Second Edition), 2013 Scaffold-Associated Proteins
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