Abstract Transcription initiation by RNA polymerase II (RNAP II) requires interaction between cis-acting promoter elements and trans-acting factors. The eukaryotic promoter consists of core elements that include the TATA box and other DNA sequences that define transcription start sites, and regulatory elements that either enhance or repress transcription in a gene-specific manner. The core promoter is the site of assembly of the transcription preinitiation complex (PIC), which includes RNAP II and the general transcription factors (GTFs) TATA-binding protein (TBP), TFIIB, TFIIE, TFIIF, and TFIIH. Regulatory elements bind gene-specific factors to affect the rate of transcription by interacting, either directly or indirectly, with components of the general transcriptional machinery. Biochemical characterization of the requirements for activation identified another class of transcription factors, designated coactivators or mediators, that are required for activation by many, but not all, activators. Accordingly, coactivators are neither gene-specific factors nor GTFs and include the SRBMED, TFHD, and SAGA complexes, as well as other factors.