Box 9.6The modular structures of RNA polymerase II promoters

The promoter for a gene transcribed by RNA polymerase II can be looked on as a series of modules, each comprising a short sequence of nucleotides and each acting as the binding site for a protein that influences assembly of the transcription initiation complex. Many different genes are transcribed by RNA polymerase II (approximately 35 000 in humans) but there are only a limited number of promoter modules. The expression pattern for a gene is therefore determined not by an individual module but by the combination of modules within its promoter, and possibly by their relative positions. The amount of transcription initiation that occurs is dependent on which modules are occupied by their binding proteins at a particular time.

The modules can be categorized in various ways. One scheme is as follows:

  • The core promoter modules (Section 9.2.2). The most important of these are the TATA box (consensus 5′-TATAWAW-3′, where W is A or T) and the Inr sequence (consensus 5′-YYCARR-3′, where Y is C or T, and R is A or G).
  • Basal promoter elements are modules that are present in many promoters and set the basal level of transcription initiation, without responding to any tissue-specific or developmental signals. These include: the CAAT box (consensus 5′-GGCCAATCT-3′), recognized by the activators NF-1 and NF-Y; the GC box (consensus 5′-GGGCGG-3′) recognized by the Sp1 activator; and the octamer module (consensus 5′-ATGCAAAT-3′), recognized by Oct-1.
  • Response modules are found upstream of various genes and enable transcription initiation to respond to general signals from outside of the cell. Examples are: the cyclic AMP response module CRE (consensus 5′-WCGTCA-3′), recognized by the CREB activator; the heat-shock module (consensus 5′-CTNGAATNTTCTAGA-3′), recognized by HSP70 and other activators; and the serum response module (consensus 5′-CCWWWWWWGG-3′), recognized by the serum response factor.
  • Cell-specific modules are located in the promoters of genes that are expressed in just one type of tissue. Examples include: the erythroid module (consensus 5′-WGATAR-3′) which is the binding site for the GATA-1 activator; the pituitary cell module (consensus 5′-ATATTCAT-3′), recognized by Pit-1; the myoblast module (consensus 5′-CAACTGAC-3′), recognized by MyoD; and the lymphoid cell module or σB site (consensus 5′-GGGACTTTCC-3′), recognized by NF-σB. Note that in lymphoid cells the octamer module is recognized by the tissue-specific Oct-2 activator.
  • Modules for developmental regulators mediate expression of genes that are active at specific developmental stages. Two examples in Drosophila are (Section 12.3.3): the Bicoid module (consensus 5′-TCCTAATCCC-3′) and the Antennapedia module (consensus 5′-TAATAATAATAATAA-3′).

The human insulin gene (shown below) illustrates the modular structure of a promoter for RNA polymerase II.

As well as the modules in the region immediately upstream of the gene, the same and other modules can also be contained within enhancers, which are 200–300 bp in length and can be located some distance upstream or downstream of their target gene. A single enhancer can influence transcription initiation of a variety of genes located within a single functional domain (Section 8.1.2). Silencers are similar to enhancers but, as their name suggests, their modules have a negative rather than enhancing influence on transcription initiation.

The modular interpretation of promoter structure is a well-established and useful concept, but its limitations must always be kept in mind. It emphasizes the role of sequence-specific DNA-binding proteins in genome expression and downplays the influence of proteins that either do not bind specifically to the genome, or whose binding sites lie distant from the genes whose expression they influence. The module concept therefore draws attention away from histone-modifying enzymes, nucleosome remodeling complexes, and other proteins that play a critical role in genome expression.

Image ch9fb3.jpg

From: Chapter 9, Assembly of the Transcription Initiation Complex

Cover of Genomes
Genomes. 2nd edition.
Brown TA.
Oxford: Wiley-Liss; 2002.
Copyright © 2002, Garland Science.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.