Enhancer-Mediated Formation of Nuclear Transcription Initiation Domains.

Enhancers in higher eukaryotes and upstream activating sequences (UASs) in yeast have been shown to recruit components of the RNA polymerase II (Pol II) transcription machinery. At least a fraction of Pol II recruited to enhancers in higher eukaryotes initiates transcription and generates enhancer RNA (eRNA). In contrast, UASs in yeast do not recruit transcription factor TFIIH, which is required for transcription initiation. For both yeast and mammalian systems, it was shown that Pol II is transferred from enhancers/UASs to promoters. We propose that there are two modes of Pol II recruitment to enhancers in higher eukaryotes. Pol II complexes that generate eRNAs are recruited via TFIID, similar to mechanisms operating at promoters. This may involve the binding of TFIID to acetylated nucleosomes flanking the enhancer. The resulting eRNA, together with enhancer-bound transcription factors and co-regulators, contributes to the second mode of Pol II recruitment through the formation of a transcription initiation domain. Transient contacts with target genes, governed by proteins and RNA, lead to the transfer of Pol II from enhancers to TFIID-bound promoters.

Regulation of RNA Polymerase II Transcription Initiation and Elongation by Transcription Factor TFII-I.

Transcription by RNA polymerase II (Pol II) is regulated by different processes, including alterations in chromatin structure, interactions between distal regulatory elements and promoters, formation of transcription domains enriched for Pol II and co-regulators, and mechanisms involved in the initiation, elongation, and termination steps of transcription. Transcription factor TFII-I, originally identified as an initiator (INR)-binding protein, contains multiple protein-protein interaction domains and plays diverse roles in the regulation of transcription. Genome-wide analysis revealed that TFII-I associates with expressed as well as repressed genes. Consistently, TFII-I interacts with co-regulators that either positively or negatively regulate the transcription. Furthermore, TFII-I has been shown to regulate transcription pausing by interacting with proteins that promote or inhibit the elongation step of transcription. Changes in TFII-I expression in humans are associated with neurological and immunological diseases as well as cancer. Furthermore, TFII-I is essential for the development of mice and represents a barrier for the induction of pluripotency. Here, we review the known functions of TFII-I related to the regulation of Pol II transcription at the stages of initiation and elongation.