Recent progress in understanding higher-order chromatin organization in the nucleus has been considerable.From single gene to chromosome territory, realistic biophysical models can now accurately predict some of the structural feature of cell nuclei. Despite growing evidence of a deterministic nuclear organization, the physiological consequence of spatial genome organization is still unclear. In the simple eukaryotic model, Saccharomyces cerevisiae, clear correlation between gene position and transcription has been established. In this review, we will focus on higher-order chromatin organization in yeast with respect to the nuclear envelope and nucleolus. In Arabidopsis thaliana, a model plant for which we have a complete genome sequence, chromosome territory (CT) arrangement and somatic homologous pairing in interphase nuclei seem to occur randomly. Since chromosomes containing nucleolar organizer regions associate more frequently to form a single nucleolar structure, as in yeast, the nucleolus seems to play a major role in organizing nuclear space. Recent findings have begun to elucidate how plant regulatory factors, such as chromatin remodeling or histone chaperones, affect the chromatin state of ribosomal DNA genes located in two distinct CT arrangements in the nucleus. The functional outcome of yeast nuclear organization allowed us to propose how nuclear organization might contribute to a novel type of epigenetic regulation: the spatial regulation of transcription.