Linkages of nuclear architecture to biological and pathological control ofgene expression

Functional interrelationships between components of nuclear architecture an d control of gene expression are becoming increasingly evident. There is gr owing appreciation that multiple levels of nuclear organization integrate t he regulatory cues that support activation and suppression of genes as well as the processing of gene transcripts. The linear organization of genes an d promoter elements provide the potential for responsiveness to physiologic al regulatory signals. Parameters of chromatin structure and nucleosome org anization support synergism between activities at independent regulatory se quences and render promoter elements accessible or refractory to transcript ion factors. Association of genes, transcription factors, and the machinery for transcript processing with the nuclear matrix facilitates fidelity of gene expression within the three-dimensional context of nuclear architectur e. Mechanisms must be defined that couple nuclear morphology with enzymatic parameters of gene expression. The recent characterization of factors that mediate chromatin remodeling and intranuclear targeting signals that direc t transcription factors to subnuclear domains where gene expression occurs, reflect linkage of genetic and structural components of transcriptional co ntrol. Nuclear reorganization and aberrant intranuclear trafficking of tran scription factors for developmental and tissue-specific control that occurs in tumor cells and in neurological disorders provides a basis for high res olution diagnostics and targeted therapy. (C) 1998 Wiley-Liss, Inc.