What do Transcription Factors Interact With?. Issue 14 (9th July 2021) - Chen, Haining
Graphical abstract: Promoter activation. TFs bind to their cognate sequences in enhancers and promoters, where they coalesce cofactors to increase chromatin accessibility and assembly of the transcription machinery. Highlights: Transcription factors (TFs) engage in three main levels of regulation. TFs target chromatin remodelers and modifiers to regulate DNA access. TFs target initiation factors like TFIID, although not widespread in yeast. TFs target Mediator to augment Pol II loading at promoters. Abstract: Although we have made significant progress, we still possess a limited understanding of how genomic and epigenomic information directs gene expression programs through sequence-specific transcription factors (TFs). Extensive research has settled on three general classes of TF targets in metazoans: promoter accessibility via chromatin regulation (e.g., SAGA), assembly of the general transcription factors on promoter DNA (e.g., TFIID), and recruitment of RNA polymerase (Pol) II (e.g., Mediator) to establish a transcription pre-initiation complex (PIC). Here we discuss TFs and their targets. We also place this in the context of our current work with Saccharomyces (yeast), where we find that promoters typically lack an architecture that supports TF function. Moreover, yeast promoters that support TF binding also display interactions with cofactors like SAGA and Mediator, but not TFIID. It is unknown to what extent all genes in metazoans require TFs and their cofactors.