Unexpected roles for core promoter recognition factors in cell-type-specific transcription and gene regulation

Abstract

The eukaryotic core promoter recognition complex was generally thought to play an essential but passive role in the regulation of gene expression. However, recent evidence now indicates that core promoter recognition complexes together with 'non-prototypical' subunits may have a vital regulatory function in driving cell-specific programmes of transcription during development. Furthermore, new roles for components of these complexes have been identified beyond development; for example, in mediating interactions with chromatin and in maintaining active gene expression across cell divisions.

Figure 1. Core promoter recognition by TFIID

Multiple subunits of the TFIID (transcription factor IID) complex bind core promoter elements. TBP (TATA binding protein) binds TATA boxes. TAF1 (TBP associated factor 1) and TAF2 (TBP associated factor 2) bind the initiator element (Inr). TAF6 (TBP associated factor 6) and TAF9 (TBP associated factor 9) bind the downstream promoter element (DPE).

Figure 2. Roles of TRFs and TAFs in germ cell differentiation

(a) Overview of mouse spermatogenesis. TRF2 (TBP related factor 2), TAF4b (TBP associated factor 4b), and TAF7L (TBP associated factor 7L) are expressed where indicated and the effect of knocking out each of these factors is shown–,–. (b) Overview of a subset of the stages of mouse oogenesis. TRF3 and TAF4b are thought to be expressed where indicated and the effect of knocking out each of these factors is shown,,,. In the case of TAF4b, knockout could affect multiple stages; the last of these stages is indicated.

Figure 3. Roles of TRF3 and TAF3 in somatic cell differentiation

(a) TRF3 (TBP related factor 3) and TAF3 (TBP associated factor 3) function in hematopoiesis. During embryogenesis in zebrafish, TRF3 and TAF3 associate with the core promoter of the mespa gene, which encodes a transcription factor that is critical for hematopoiesis,. (b) Proposed TRF3 and TAF3 function in myogenesis. When mouse myoblasts differentiate into myotubes, levels of multiple TFIID subunits decrease,. By contrast, TAF3 levels remain constant, as do levels of TRF3. TRF3 and TAF3 form a complex in myotubes and are found together at the promoter of the myogenin gene, which encodes a transcriptional activator that is critical for myogenesis.

Figure 4. TBP bookmarks genes during mitosis

In mitotic nuclei, TBP (TATA binding protein) binds protein phosphatase 2A (PP2A) and the CAP-G subunit of condensin at the core promoters of genes that were active prior to mitosis. PP2A dephosphorylates CAP-G, which inactivates condensin and keeps the core promoters from being tightly compacted in mitotic chromatin. This allows transcription of the bookmarked genes to be reactivated when cells exit mitosis and enter G1. During mitosis Pol II leaves chromatin and genes are transcriptionally inactive. Whether any general transcription factors (GTFs) other than TBP remain at bookmarked genes is unknown.