The molecular pathways that participate in regulation of gene expression are being progressively unraveled. Extracellular signals, including the binding of extracellular matrix and soluble molecules to cell membrane receptors, activate specific signal transducers that process information inside the cell leading to alteration in gene expression. Some of these transducers when translocated to the cell nucleus may bind to transcription complexes and thereby modify the transcriptional activity of specific genes. However, the basic molecules involved in the regulation of gene expression are found in many different cell and tissue types; thus, the mechanisms underlying tissue-specific gene expression are still obscure. In this review we focus on the study of signals that are conveyed to the nucleus. We propose that the way in which extracellular signals are integrated may account for tissue-specific gene expression. We argue that the integration of signals depends on the nature of the structural organization of cells (i.e., extracellular matrix, membrane proteins, cytoskeleton, nucleus) that defines a particular cell type within a tissue. Thus, gene expression can be envisioned as being regulated by the mutual influence of extracellular and intracellular organizations, i.e., in context.