Using the osteocalcin gene as a paradigm for bone tissue-specific transcription, evidence is presented for functional linkage of nuclear architecture with developmental and steroid hormone-responsive control. The involvement of chromatin structure, nucleosome organization and the nuclear matrix is evaluated within the context of integrating regulatory signals that activate and/or suppress transcription of the osteocalcin gene. Mechanisms are evaluated which direct the bone and hematopoietic-specific acute myelogenous leukemia/core binding factor (AML/CBF) transcription factors to nuclear matrix-associated subnuclear domains that are competent to support expression.