Nuclear architecture supports integration of physiological regulatory signals for transcription of cell growth and tissue‐specific genes during osteoblast differentiation

Abstract

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 i s 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 i s 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. z 1994 WlIey-Llss, Inc

The Matrix Attachment Region-Binding Protein SATB1 Participates in Negative Regulation of Tissue-Specific Gene Expression

“…In one possible model for MMTV transcription, MARs in both LTRs bind to the nuclear matrix and, as in models proposed for other transcriptional units (39,82), loop out the intervening transcribed region. Cux/CDP and SATB1 bind to the MAR-associated NREs in the MMTV LTR.…”

“…It has been suggested that binding to the nuclear matrix is a prerequisite for gene transcription and that MARs function to anchor genes to the nuclear matrix, a structure rich in transcription factors (39,82). In one possible model for MMTV transcription, MARs in both LTRs bind to the nuclear matrix and, as in models proposed for other transcriptional units (39,82), loop out the intervening transcribed region.…”

The nuclear matrix protein NMP-1 is the transcription factor YY1.

“…The nuclear matrix has been linked to multiple functions that mediate the control of gene expression within the nucleus (1)(2)(3)(4)(5)(6)(7)(8). This component of the nuclear architecture provides the internal scaffold of the nucleus; it consists of a peripheral lamina-pore complex, an internal filamentous ribonucleoprotein network, and residual nucleoli (2,8).…”

ATP-Dependent Release of Glucocorticoid Receptors from the Nuclear Matrix

“…Although specific MAR-binding proteins have been identified (18,77), their role in mediating the tissue-and cell-type-specific binding of active genes to the nuclear matrix is not understood. A number of transcription factors have been found to be associated with the nuclear matrix (6,73,76) and appear to differentially partition between the matrix and an extractable compartment of the nucleus, depending on such variables as tissue type and growth conditions (70). Therefore, it seems likely that specific mechanisms exist to regulate the exchange of transcription factors between the nuclear matrix and soluble compartments of the nucleus.…”