Eukaryotic protein‐coding genes are typically classified into two groups: those with expression regulated by specific signals versus the relatively constant “housekeeping” genes. Although these differences are associated with alternative modes of RNA polymerase II (RNAP II) pre‐initiation complex (PIC) assembly, a role for gene‐specific activators in controlling “regulatability” has been difficult to rule out. To address this question, de Jonge et al (2017) studied a group of genes controlled by a common activator but dependent on either TFIID or SAGA and found that the magnitude of regulation strongly correlates with the mechanism of PIC assembly.
See also: WJ de Jonge et al (February 2017)
Studies over the past 40 years have led to the view that important mechanistic differences exist at the level of transcription initiation between genes whose expression is highly regulated and those whose transcription rates are relatively constant, referred to as “housekeeping genes” (Eisenberg & Levanon, 2013). Core promoters of highly regulated genes typically contain a canonical “TATA element”, the binding site for TATA‐binding protein (TBP), a key general transcription factor (TF) required for PIC assembly whose association with DNA is aided by the multifunctional SAGA complex. In contrast, at housekeeping genes, the TATA element is less conserved (“TATA‐like”) and TBP is recruited to these promoters in the context of the TFIID, a large complex containing multiple TBP‐associated factors (TAFs) (see Fig 1). These associations suggest that the two modes of TBP binding may be directly responsible for the observed differences in regulatory amplitude. Another explanation is that the differences result from some property of the gene‐specific activators operating at the two classes of genes. Distinguishing between …
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