Response element

Some transcription control mechanisms can be categorized based on a common response to certain metabolic factors. Enhancers that respond to these factors are called response elements. Examples include the heat-shock element (HSE), the glucocorticoid-response element (GRE), the metal-response element (MRE), and the cyclic-AMP-response element (GRE). 

These response elements all bind proteins (transcription factors) that are produced under certain cell conditions, and several related genes are activated. This is not the same as an operon because the genes are not linked in sequence and are not controlled by a single promoter. Several different genes, all with unique promoters, may all be affected by the same transcription factor binding the response element. 

In the case of HSE, elevated temperatures lead to the production of specific heat-shock transcription factors that activate the associated genes. Glucocorticoid hormones bind to a steroid receptor. Once bound, this becomes the transcription factor that binds to the GRE. Table 11.4 summarizes some of the best-understood response elements. 

We will look more closely at the cyclic-AMP-response element as an example of eukaryotic control of transcription. Hundreds of research papers deal with this topic as more and more genes are found to have this response element as part of their control. Remember that cAMP was also involved in the control of prokaryotic operons via the GAP protein. 

Gyclic AMP is produced as a second messenger from several hormones, such as epinephrine and glucagon (see Chapter 24). When the levels of cAMP rise, the activity of cAMP-dependent protein kinase (protein kinase A) is stimulated. This enzyme phosphorylates many other proteins and enzymes inside the cell 

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Biosynthesis. CRE is derived from a precursor of 196 amino acids (84,85). This gene contains one copy of CRE, which is flanked by double basic amino acids. The amino acid sequence of the CRE precursor suggests that it may arise from proteins related to POMC and neurophysins (31). The CRE precursor contains a cAMP responsive element which aHows stimulation of mRNA synthesis when intraceHular levels of cAMP are increased (86). 

More subtle modes of action are also possible since the response to hormone receptor binding is complex and could be affected by chemical interference with receptor-related proteins, DNA methylation or histone acetylation. Dioxin (TCDD), for example, reduces the ability of the oestrogen-receptor complex to bind to the oestrogen response element of DNA, reducing gene transcription. ... 

In summary, a DNA-supported asymmetric interface located within the DNA-binding domains of these nuclear receptors provides the molecular basis for receptor heterodimers to distinguish between closely related response elements. RXR can provide a repertoire of different dimerization surfaces, each one unique for a specific partner, allowing dimers to form that are adapted to the length of the spacer region in their corresponding response elements. 

Figure 10.12 Response elements for heterodimers of the nuclear receptor for ds-retinoic acid (RXR) with the receptors for vitamin D (VDR), thyroid hormone (TR) and trans-retinoic acid (RAR). The half-sites of these response elements have identical nucleotide sequences and are organized as direct repeats. They differ in the number of base pairs in the spacer region between the half-sites. This difference forms the basis for the ability of the heterodimers to discriminate between the different response elements.

Schwabe, J.W.R., et al. The crystal structure of the estrogen receptor DNA-binding domain bound to DNA how receptors discriminate between their response elements. Cell 75 567-578, 1993. 

According to the operational model, the response producing species activate the response elements of the cell according to... 

Cyclic adenosine monophosphate, 25f Cyclic adenosine monophosphate response element binding, 83, 88 Cytochrome P450 enzymes, 171... 

One such hypotheses submits that most antidepressants enhance the expression of cyclo-AMP response element binding protein (CREB), which is a transcription factor that after phosphorylation binds to cyclo-AMP response elements localized in the promoter region of many genes including that coding for brain... 

CREB stands for cyclic-AMP response element (CRE) binding protein and is a transcription factor. When phosphorylated by cyclic AMP- and cyclic GMP-dependent Protein Kinases or other protein kinases it binds to gene promoters that contain a specific binding site. After binding, the respective transcription activity is modulated. 

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