Compartmentalization and compaction of DNA in the nucleus is the characteristic feature of eukaryotic cells. A fully extended DNA molecule has to be compacted 100,000 times to fit within the nucleus. At the same time it is critical that various DNA regions remain accessible for interaction with regulatory factors and transcription/replication factories. This puzzle is solved at the level of DNA packaging in chromatin that occurs in several steps: rolling of DNA onto nucleosomes, compaction of nucleosome fiber with formation of the so-called 30 nm fiber, and folding of the latter into the giant (50-200 kbp) loops, fixed onto the protein skeleton, the nuclear matrix. The general assumption is that DNA folding in the cell nucleus cannot be uniform. It has been known for a long time that a transcriptionally active chromatin fraction is more sensitive to nucleases; this was interpreted as evidence for the less tight compaction of this fraction. In this review we summarize the latest results on structure of transcriptionally active chromatin and the mechanisms of transcriptional regulation in the context of chromatin dynamics. In particular the significance of histone modifications and the mechanisms controlling dynamics of chromatin domains are discussed as well as the significance of spatial organization of the genome for functioning of distant regulatory elements.