What do Transcription Factors Interact With?

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.

Keywords: enhancers; gene regulation models; promoters; transcription mechanisms.

Fig. 1.. Simplified model of enhancer-core promoter interactions.

Enhancers contain specific sequence motifs that are bound by TFs . They activate core promoters by regulating promoter/enhancer interactions, PIC assembly, and Pol II recruitment through a wide variety of cofactors.

Fig. 2.. Condensate-based model of enhancer-promoter control.

TFs with their intrinsically disordered regions (IDRs) along with other IDRs in cofactors coalesce and demix, thereby dramatically increasing the local concentration of components of the transcription machinery. Potential consequences include increased nucleosome dynamics affecting enhancer/promoter accessibility, more frequent PIC assembly, and a steady stream of Pol II loading and firing into an elongation complex.

Fig. 3.. Binary architecture of yeast promoters.

Summary schematic of yeast chromatin structures with key architectural arrangements at constitutive (upper) and induced (lower) promoter classes. T, A, B, E, F, H denote TBP, TFIIA, TFIIB, TFIIE, TFIIF, and TFIIH, respectively. NFR and NDR denote nucleosome-free region and nucleosome-depleted region, respectively.