The spatial organization of eukaryotic genomes in the cell nucleus is linked to their transcriptional regulation. In mammals, on which this review will focus, transcription-related chromatin positioning is regulated at the level of chromosomal sub-domains and individual genes. Most of the chromatin remains stably positioned during interphase. However, some loci display dynamic relocalizations upon transcriptional activation, which are dependent on nuclear actin and myosin. Transcription factors in association with chromatin modifying complexes seem to play a central role in regulating chromatin dynamics and positioning. Recent results obtained in this regard also give insight into the question how the different levels of transcriptional regulation are integrated and coordinated with other processes involved in gene expression. Corresponding findings will be discussed.