The nucleus is a highly heterogeneous structure, containing various 'landmarks' such as the nuclear envelope and regions of euchromatin or dense heterochromatin. At a morphological level, regions of the genome that are permissive or repressive to gene expression have been associated with these architectural features. However, gene position within the nucleus can be both a cause and a consequence of transcriptional regulation. New results indicate that the spatial distribution of genes within the nucleus contributes to transcriptional control. In some cases, position seems to ensure maximal expression of a gene. In others, it ensures a heritable state of repression or correlates with a developmentally determined program of tissue-specific gene expression. In this review, we highlight mechanistic links between gene position, repression and transcription. Recent findings suggest that architectural features have multiple functions that depend upon organization into dedicated subcompartments enriched for distinct enzymatic machinery.