Core promoters

The DNA part of each control module can be divided into three main regions, the core or basal promoter elements, the promoter proximal elements and the distal enhancer elements (Figure 9.1). The best characterized core promoter element is the TATA box, a DNA sequence that is rich in A-T base pairs and located 25 base pairs upstream of the transcription start site. The TATA box is recognized by one of the basal transcription factors, the TATA box-binding protein, TBP, which is part of a multisubunit complex called TFIID. This complex in combination with RNA polymerase 11 and other basal transcription factors such as TFIIA and TFIIB form a preinitiation complex for transcription. 

The general transcription factor TFllD is believed to be the key link between specific transcription factors and the general preinitiation complex. However, the purification and molecular characterization of TFllD from higher eucaryotes have been hampered by its instability and heterogeneity. All preparations of TFllD contain the TATA box-binding protein in combination with a variety of different proteins called TBP-associated factors, TAFs. When the preinitiation complex has been assembled, strand separation of the DNA duplex occurs at the transcription start site, and RNA polymerase II is released from the promoter to initiate transcription. However, TFIID can remain bound to the core promoter and support rapid reinitiation of transcription by recruiting another molecule of RNA polymerase. 

General or basic transcription factors are required for every gene to allow the proper recruitment of RNA polymerases to ensure transcriptional activity. They bind to core promoters in the vicinity of transcriptional start sites in a sequential manner. 

White, D. M., et al. (1997). Beta-trace gene expression is regulated by a core promoter and a distal thyroid hormone response element. J. Biol. Chem. 272, 14387-93. Yamashima, T., et al. (1997). Prostaglandin D synthase (beta-trace) in human... 

Lomvardas, S. and Thanos, D. (2002) Modifying gene expression programs by altering core promoter architecture. Cell 110, 261-271. 

Novina CD, Roy AL (1996), Core promoters and transcriptional control, Trends Genet. 12 351-355. 

The 5 end of MT-1 and MT-2 genes possess a TATA box, or core promoter element and numerous response elements that confer metal inducibility on the MT gene promoter (Figure 21.8). Some of these response elements such as API and AP2 in humans and in mouse, the antioxidant response element (ARE) and upstream stimulatory factor (USF) provide putative binding sites for MT transcription factors. The most common of these cis-acting proximal elements are the metal responsive elements (MREs), motifs that are conserved across vertebrate and invertebrate species. Multiple copies of MREs exist in the MT promoter region and act syner-gistically to enhance activity. 

J.M. Park, B.S. Gim, J.M. Kim, J.H. Yoon, H.S. Kim, J.G Kang, and Y.J. Kim. 2001. Drosophila mediator complex is broadly utilized by diverse gene-specific transcription factors at different types of core promoters Mo/. Cell. Biol. 21 2312-2323. (PubMed) (Full Text in PMC)... 

S. T. Smale, A. Jain, J. Kaufmann, K.H. Emami, K. Lo, and LP. Garraway. 1998. The initiator element A paradigm for core promoter heterogeneity within metazoan protein-coding genes Cold Spring Harbor Symp. Quant. Biol. 63 21-31. (PubMed)... 

T.W. Burke, P.J. Willy, A.K. Kutach, J.E. Butler and J.T. Kadonaga. The DPE, a conserved downstream core promoter element that is functionally analogous to the TATA box. Cold Spring Harb. Symp. Quant. Biol. 63 (1998) 75-82. 

A simplified diagram of transcription is shown here. Double-stranded DNA (dsDNA) is shown as a long rectangle. RNA polymerase binds to a region of DNA called a core promoter The core promoter consists of all the DNA between the TATA sequence and the transcription start site. The core promoter is a short stretch of DNA that serves to bind and orient RNA polymerase, and the basal transcription factors. The TATA sequence, which is composed of only four nucleotides T A, T, and A), usually occurs about 25 base pairs upstream of the transcription start site. The TATA-binding protein is a special protein that binds to the TATA sequence prior to initiating transcription. 

The promoter of STSSia I (GD3-synthase, STII), which has attracted much more attention than have other promoters of the ganglioside synthase genes, has been cloned from rat [103], mouse [104] and human [105]. The promoter of all three species is TATA-less and does not possess known core- promoter elements, including the initiator (INR), the downstream promoter (DPE), the TFIIB recognition elements (BRE), and the motif ten element (MTE). Similar to other TATA-less promoters, it has a high GC content and is enriched in Spl-bind-ing sites. The proximal promoter region is defined within 500 or 700 bp upstream of the ATG... 

Yang C, Bolotin E, Jiang T, Sladek FM, Martinez E (2007) Prevalence of the initiator over the TATA box in human and yeast genes and identification of DNA motifs enriched in human TATA-less core promoters. Gene 389 52-65... 

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