Promoting developmental transcription

Abstract

Animal growth and development depend on the precise control of gene expression at the level of transcription. A central role in the regulation of developmental transcription is attributed to transcription factors that bind DNA enhancer elements, which are often located far from gene transcription start sites. Here, we review recent studies that have uncovered significant regulatory functions in developmental transcription for the TFIID basal transcription factors and for the DNA core promoter elements that are located close to transcription start sites.

Fig. 1.

Cis-acting DNA transcription-regulatory elements. (A) The generic organization of transcription-regulatory regions of a eukaryotic gene, depicting the organization and location of enhancer, proximal promoter, and core promoter elements, as well as the regulatory factors that bind these elements. (B) Promoter structure of the mouse Myog gene, which is used as an example throughout the text. Known elements in the core and proximal promoter regions are indicated.

Fig. 2.

Eukaryotic transcription initiation patterns. High-throughput genomic data on transcription start sites (TSSs) allows different transcription initiation patterns to be visualized and analyzed. Two different embryonic initiation patterns for genes with previously mapped TSSs are shown, adapted from the MachiBase database browser, which contains high-throughput sequence read data from Drosophila libraries of 5′ capped transcripts (Ahsan et al., 2009). These displays show (top) the coordinates of a selected genomic region, followed (middle) by the gene structure annotations and transcript data for this region from FlyBase: first, transcripts with FlyBase transcript (FBtr) IDs; then, expressed sequence tag (EST) evidence (for the purposes of clarity, the displays only show a selection of tags that map to the region). Finally (bottom), the distribution of embryonic 5′ reads in the selected region that align to the same genomic location are shown (read numbers are on a logarithmic scale). (A) The Gapdh2 (Glyceraldehyde-3-phosphate dehydrogenase 2) gene on chromosome 2R exhibits a peaked initiation pattern, in which most transcription events originate from a small genomic region (Tso et al., 1985). (B) The PCNA [proliferating cell nuclear antigen, also known as mutagen sensitive 209 (mus209)] gene on chromosome 2R exhibits a broad pattern, in which initiation events are spread out over a larger genomic region of typically 100-200 nucleotides (Hochheimer et al., 2002). These examples demonstrate that the major sites of transcription initiation do not necessarily correspond to the 5′ ends of transcripts annotated in genomic databases, but that they are often supported by existing transcript evidence in the form of ESTs.

Fig. 3.

Core promoter element configurations. (A) Promoters with canonical position-specific elements. (Top) The relative locations of known elements (see Table 1). (Middle) fushi tarazu (ftz) contains an Inr, a TATA box and DPE. ftz activation by Caudal is primarily dependent on the DPE site (Juven-Gershon et al., 2008). (Bottom) Tollo contains both of the Drosophila downstream elements, the MTE and DPE, which both contribute to transcriptional activation (Lim et al., 2004). (B) Promoters with non-position-specific elements. (Top) The Drosophila genes encoding histones H2A, H2B, H3 and H4 have canonical TATA boxes, but (middle) the H1 gene is TRF2 dependent and not bound by TBP (Isogai et al., 2007a). TRF2 is a conserved TBP-replacing factor, which does not directly associate with DNA but rather interacts with specific transcription factors, such as DREF, which binds the DRE (Hochheimer et al., 2002). (Bottom) TBP- and TRF2-dependent promoters can regulate the same gene via alternative TSSs, as is the case for PCNA, in which one TSS is TRF2 dependent via its interaction with DREF, and a second downstream promoter is TBP dependent (Hochheimer et al., 2002). Only experimentally validated elements are shown.

Fig. 4.

General functions of TFIID and mechanisms that regulate the diversity of TFIID subunits. (A) The general functions of TFIID that facilitate transcription initiation by Pol II. (B) The general mechanisms by which the structure and function of TFIID are modified. Specific examples are described in the text.