Mammalian genomes are partitioned in chromosomes and contain millions of base pairs that encode for tens of thousands of protein-coding genes ( approximately 30,000 in humans) and many more non-coding transcripts. Gene forests interspersed with gene deserts in the linear DNA sequence may segregate into domains that are more or less permissive for transcription within the three-dimensional nucleus. Functional attachments to various nuclear landmarks are thought to organise the architectural folding of the chromosome fibre. The position of a gene within the nucleus can favour its silencing or activation and the efficiency with which its products are processed or transported to the cytoplasm. The stochastic properties of genome organisation may contribute to cell-type-specific gene expression and to the dynamic responses that occur during differentiation and adaptation to the environment. The first steps for high-throughput mapping of chromosome architecture in specific cell types are under way to help understand the mechanisms by which genome architecture may regulate gene expression.