Of the approximately 21,000 protein-coding genes in human cells, only a fraction of these are expressed in any one cell type, or at any particular time in development, or at any one stage in the cell cycle. The ability for a gene to be transcribed depends on the presence of numerous proteins.
The workhorse protein in the transcription process is, of course, RNA polymerase—specifically, RNA polymerase II for protein-coding genes. RNA polymerase II creates a complementary RNA strand from the code in a DNA template strand. However, RNA polymerase II is unable to bind to DNA and begin transcription on its own. It requires other proteins, called transcription factors, to come into play. In the accompanying animation, we examine the events of transcription initiation in eukaryotes, highlighting the various transcription factors, regulatory proteins, and DNA regions that play important roles in the process.
In eukaryotes, a number of proteins, called transcription factors, must bind to a promoter before RNA polymerase II can bind and initiate transcription. The first transcription factor to bind has been named TFIID. TFIID binds to a region of the promoter called the TATA box, which contains the sequence TATAT.
Following TFIID binding, a succession of other transcription factors and RNA polymerase II bind, forming an initiation complex.
Although this complex is often capable of initiating transcription, for many genes, other proteins are required for a high rate of transcription. In the promoter, there may be a region of DNA that can bind to regulator proteins. A regulator protein binds to the regulator region and to the transcription initiation complex, thereby activating it.
Enhancer regions are yet other transcriptionally important regions on the DNA, and they are frequently located some distance from the promoter, often tens of thousands of base pairs away. Activator proteins bind to enhancers, and then attach to the transcription-initiation complex, stimulating it strongly.
If a cell has all of the appropriate DNA sequences, and if all the necessary regulator proteins and transcription factors are present and in place, transcription begins and the gene is expressed. Otherwise, no transcription or very little transcription takes place, and the gene is silent.
In the accompanying animation, we examined the formation of a transcription initiation complex in eukaryotes. Protein-coding genes in eukaryotes require the formation of this complex in order for transcription to begin. In addition, many genes also require the binding of regulator and activator proteins. The presence of such proteins in a cell thus determines whether a gene is transcribed.
For example, in the immature red blood cells of bone marrow, which make a large amount of β-globin, the transcription of globin genes is stimulated by the binding of 7 regulators and 6 activators. But in white blood cells in the same bone marrow, these 13 proteins are not made, and therefore they cannot bind to their sites adjacent to the β-globin genes; consequently, these genes are hardly transcribed at all.