MoBio Enhancer Chapter 4

Enhancer is the DNA element that, upon binding with transcription factors (activators), can enhance transcription. It may be located either upstream or downstream of the transcriptional initiation site. However, most of them are located upstream. In prokaryotes, enhancers are quite close to the promoter, but eukaryotic enhancers could be far from the promoter. A few examples are given below.

E. coli glnA gene
Image

The enhancer of the glnA gene is located about 120 bp from the start site, containing two binding sites for the transcription factor nitrogen regulatory protein C (NTRC).

Yeast GAL1 and GAL10 genes
Image

Both GAL1 and GAL10 genes are regulated by the same enhancer between them. The two genes are transcribed along opposite directions. Therefore, the enhancer is located upstream of both transcriptional start sites. It is also called upstream activating sequences (UAS), which contains four binding sites of the transcription factor GAL4.

Human β globin gene cluster
Image

The human β globin gene cluster is controlled by an enhancer region comprising HS1 to HS4, which contain the binding sites of GATA-1, NF-E2, AP-1 and other transcriptional activators. This region is known as the locus control region (LCR), which regulates the expression of all five genes (ε, Gγ, Aγ, δ and β), even though the distance between HS4 and the β gene is as far as 60 kb.

In embryonic DNA, the ε gene is preferentially expressed. In fetal DNA, Gγ and Aγ are much more strongly expressed than the other genes. In adult DNA, expression is switched to mainly the β gene, while the δ gene is weakly expressed.

 

Table 4-C-3. Examples of transcriptional activators in mammals.

Transcription
Activator
Consensus
Sequence
Transcription
Activator
Consensus
Sequence
AP-1 TGAGTCA p53 PuGPuCATGPyCPy
AP-2 CCC(A/C)N(C/G)3 NF-kB GGGPuNTPyPyCC
Oct-1 ATGCAAAT NFAT GGAGAPu
GATA-1 (A/T)GATAPu NF-E2 TGACTCAG

*Pu = Purine (A or G); Py = Pyrimidine (C or T); N = any.