The regulation of transcription in eukaryotes is considerably more complex than in other domains of life. The polymerase responsible for the transcription of protein-coding genes, pol II, is regulated at many levels, including initiation, promoter-proximal pause, elongation, and termination. Many regulatory steps occur at the level of formation of the pre-initiation complex. Enhancers and coregulators, such as the mediator, play critical roles at this stage. Many transcription factors bind to enhancers, and this enhancer-assembled complex plays a fundamental role in controlling many aspects of transcription. Once the polymerase enters the elongation phase, the promoter-proximal pause ensues. The promoter-proximal pause is highly regulated. Two major outcomes are possible, premature termination or entry into processive elongation. An important transcription termination-related regulatory process, alternative polyadenylation, will be dealt with in a later chapter.