During the past several years it has become increasingly evident that the three-dimensional organization of the nucleus plays a critical role in transcriptional control. The principal theme of this prospect will be the contribution of nuclear structure to the regulation of gene expression as functionally related to development and maintenance of the osteoblast phenotype during establishment of bone tissue-like organization. The contributions of nuclear structure as it regulates and is regulated by the progressive developmental expression of cell growth and bone cell related genes will be examined. We will consider signalling mechanisms that integrate the complex and interdependent responsiveness to physiological mediators of osteoblast proliferation and differentiation. The focus will be on the involvement of the nuclear matrix,
chromatin structure, and
nucleosome organization in transcriptional control of cell growth and bone cell related genes. Findings are presented which are consistent with involvement of nuclear structure in gene regulatory mechanisms which support osteoblast differentiation by addressing four principal questions: 1) Does the representation of
nuclear matrix proteins reflect the developmental stage-specific requirements for modifications in transcription during osteoblast differentiation? 2) Are developmental stage-specific
transcription factors components of
nuclear matrix proteins? 3) Can the nuclear matrix facilitate interrelationships between physiological regulatory signals that control transcription and the integration of activities of multiple promoter regulatory elements? 4) Are alterations in gene expression and cell phenotypic properties in transformed osteoblasts and
osteosarcoma cells reflected by modifications in
nuclear matrix proteins? There is a striking representation of
nuclear matrix proteins unique to cells, tissues as well as developmental stages of differentiation, and tissue organization. Together with selective association of regulatory molecules with the nuclear matrix in a growth and differentiation-specific manner, there is a potential for application of
nuclear matrix proteins in
tumor diagnosis, assessment of
tumor progression, and prognosis of
therapies where properties of the transformed state of cells is modified. It is realistic to consider the utilization of
nuclear matrix proteins for targeting regions of cell nuclei and specific genomic domains on the basis of developmental phenotypic properties or tissue pathology.