Transcription initiation by RNA polymerase II at eukaryotic protein-coding genes involves the cooperative assembly on the core promoter of multiple distinct proteins, including RNA polymerase II itself and basal transcription factors, to form a stable basal... Transcription initiation by RNA polymerase II at eukaryotic protein-coding genes involves the cooperative assembly on the core promoter of multiple distinct proteins, including RNA polymerase II itself and basal transcription factors, to form a stable basal transcriptional machinery. This assembly is a major point of control by gene-specific transcription factors (activators and repressors) and is hindered by the packaging of promoter DNA into nucleosomes and higher order chromatin structures. Transcription cofactors (coactivators and corepressors) interact with gene-specific transcription factors and/or various components of the basal transcriptional machinery and are also essential for regulated transcription. BTM, basal transcriptional machinery; HAT, histone acetyltransferase; HDAC, histone deacetylase; TRE, 12-O-tetradecanoylphorbol-13-acetate response elements. Michalis V. Karamouzis et al. Mol Cancer Res 2007;5:109-120 ©2007 by American Association for Cancer Research