Multiple levels of nuclear structure contribute to functional interrelationships with transcriptional control in vivo. The linear organization of gene regulatory sequences is necessary but insufficient to accommodate the requirements for physiological responsiveness to homeostatic, developmental, and tissue-related signals. Chromatin structure, nucleosome organization, and gene-nuclear matrix interactions provide a basis for rendering sequences accessible to transcription factors supporting integration of activities at independent promoter elements of cell cycle- and tissue-specific genes. A model is presented for remodeling of nuclear organization to accommodate developmental transcriptional control.