Enhancer Region

1983 Neuberger, 1983 Mercola et al., 1983). This enhancer is normally positioned over a thousand bp downstream of the initiation region, within the major intron. Enhancers within introns of cellular genes may also be present in the immunoglobulin K light chain gene (Queen and Baltimore, 1983). 

That enhancer regions may be more or less effective in different cell types was originally suggested by studies on polyoma virus. Wild-type virus normally multiplies well in mouse cells of many types but will not propagate in undifferentiated embryonal carcinoma cell lines due to a block in the initiation of viral transcription (Dandolo et al., 

Finally, the hormonal stimulation of transcription of the mouse mammary tumor virus (MMTV) might result from the regulation of enhancer activity. Many laboratories have carried out mutation analysis to determine which DNA sequences in the control region of MMTV are responsible for induction of viral transcription by glucocorticoids. A composite from the various laboratories indicates that 

---

Marsh S, Ameyaw MM, Githanga J et al. Novel thymidylate synthase enhancer region alleles in African populations. Hum Mutat 2000 16 528. 

VlLLAFRANCA E, OKRUZHNOV Y, DOMIN-guez MA et al. Polymorphisms of the repeated sequences in the enhancer region of the thymidylate synthase gene promoter may predict downstaging after preoperative chemoradiation in rectal cancer. J Clin Oncol 2001 19 1779-1786. 

An important factor in the resistance to chemotherapy drugs such as 5-fhiorour-acil and Raltitrexed is an increase in TS expression [72, 37]. The TS enhancer region polymorphism may be one mechanism responsible for increasing TS gene expression. 

Marsh S, Collie-Duguid ESR, Li T, Liu X, McLeod HL. Ethnic variation in the thymidylate synthase enhancer region polymorphism among Caucasian and Asian populations. Genomics 1999 58 310-312. 

This model was developed at CIEA in Japan, and the first information about the mouse was published in 1990. The mice have five or six copies of the human H-ras proto-oncogene inserted in tandem into their genome surrounded by their own promoter and enhancer regions. This transgene has been very stabile, with no loss of responsiveness since the model was developed. The transgene codes for a molecular switch protein in the same way as the previous model, but the transgene is expressed in all organs and tissues. Thus the response endpoint is not primarily dermal. 

Structural studies of the chromatin organization of integrated HlV-1 have identified two DNase 1-Hypersensitive Sites (HS4 and HS7) outside of the promoter/enhancer region in U3, that were likely to play a role in controlling viral transcription by virtue of their accessibility in chromatin (Fig. la and lb) (Verdin, 1991). 

Activator proteins (and a few repressors) are important in eukaryotes, as they are in prokaryotes. The DNA sequences to which activator proteins bind in eiikaryotic DNA are called response elements. A few response elements are located within the promoter region (upstream promoter elements [UPE]), but most are outside the promoter and often clustered to form an enhancer region that allows control of gene expression by multiple signals (Figure 1-5-4). 

Specific transcription factors bind to enhancer regions or, in a few cases, to silencers and mod-ciate the formation of the initiation complex, thus regulating the rate of initiation of transcription. Each gene contains a variety of enhancer or silencer sequences in its regulatory region. The exact combination of specific transcription factors available (and active) in a particular cell at a particular time determines which genes will be transcribed at what rates, because specific transcription factors are proteins, their expression can be cell-type specific.. Additionally, hormones may regulate the activity of some specific transcription factors. Examples include steroid receptors and the CREB protein. 

Second messengers often involved Protein kinases activated Hormone-receptor complex binds hormone response elements (HRE, of enhancer regions) inDNA... 

Once formed, 1,25-DHCC acts on duodenal epithelial cells as a lipid-soluble hormone. Its intracellular receptor (a Zn-finger protein) binds to response elements in enhancer regions of DNA to induce the synthesis of calcium-binding proteins thought to play a role in stimulating calcium uptake from the GI tract. 

Koyano, S., Kurose, K., Saito, Y., et al. (2004) Functional characterization of four naturally occurring variants of human pregnane X receptor (PXR) one variant causes dramatic loss of both DNA binding activity and the transactivation of the CYP3A4 promoter/enhancer region. Drug Metab. Dispos. 32, 149-154. 

HMGA Binding Sites on Promoter/Enhancer Regions form a Gene-Specific Bar Code ... 

Enhancer regions are af-acting elements, sequences that can also affect transcription. 

Mutations may alter regulatory sequences, eg, in promoter or enhancer regions, which can affect gene expression. 

Thymidylate Synthase Promoter Enhancer Region (TSER)... 

Fig. 3. Polymorphisms in the TS gene. Abbreviations.- TSER (thymidylate synthase enhancer region) 2R (two-tandem repeats) 3R (three-tandem repeats) TSER 3G (single nucleotide polymorphism of TSER 3R) -6bp (TS 3 -UTR 6bp deletion polymorphism). (Adapted to Marsh et al. Thymidylate synthase pharmacogenetics. Invest New Drugs 2005).

---