Information in DNA is not limited to sequence information. Both local and global conformational parameters are pivotal to the interaction with a number of relevant proteins. The function of the major components of the transcription machinery (RNA polymerase II, DNA topoisomerase I, nucleosomes, the TATA-binding factor) is dependent on the topological status of the substrate DNA molecule. The topological requirements and the conformational consensus that dictate the rules for localization of nucleosomes and define the active sites for DNA topoisomerase I have been established; the reaction of DNA topoisomerase I is regulated by a topological feedback mechanism. The integrating function of the free energy of supercoiling in the transcription process and the regulatory role of DNA topoisomerase I are discussed.