Shifting players and paradigms in cell-specific transcription

Abstract

Historically, developmental-stage- and tissue-specific patterns of gene expression were assumed to be determined primarily by DNA regulatory sequences and their associated activators, while the general transcription machinery including core promoter recognition complexes, coactivators, and chromatin modifiers was held to be invariant. New evidence suggests that significant changes in these general transcription factors including TFIID, BAF, and Mediator may facilitate global changes in cell-type-specific transcription.

Figure 1. Model of Preinitiation Complex Assembly

Sequence-specific activators (green) bind proximal (PE) and distal (DE) enhancer elements within the regulatory DNA of a gene and recruit TFIID (yellow) to the core promoter. These activators and/or TFIID in turn recruit chromatin remodeling complexes such as SWI/SNF (orange), coactivators including Mediator (MED, blue), and TFIIA and TFIIB (purple). The TFIID/TFIIA/TFIIB heterotrimer sequentially recruits TFIIE, TFIIF, PolII (red), and TFIIH (purple), allowing for promoter escape and productive transcriptional elongation.

Figure 2. Model of Cell-Type-Specific Changes in General Transcription Factors

ES cells and proliferative progenitors are believed to contain canonical TFIID consisting of TBP (red) and 12–15 associated TAFs (yellow), Mediator (blue), and ES BAF consisting of both common (orange) and ES cell-specific subunits (tan). Myotubes may replace TFIID with a novel complex of TRF (green) and TAF3 (yellow), and also downregulate Mediator and presumably retain a general BAF complex (orange). Neurons are known to contain a novel BAF complex with conserved (orange) and neuron specific subunits (purple). The disposition of Mediator and TFIID in most neuronal cell types is not known. Spermatocytes have elevated levels of TRF2 (purple) and of the TAF7 paralog TAF7l (lime) which may or may not be a component of an altered TFIID. Ovarian cells have elevated levels of TRF3 (green) and of an altered TFIID containing one or more subunits of the TAF4 paralog, TAF4b (tan). The subunit composition of Mediator and BAF complexes in germ cells is currently unknown.