Enhancer promoter interaction

Figure 13.13 Enhancer promoter interaction via protein mediated DNA loop. Enhancers are sequence elements located at varying positions, either upstream (top) or downstream (bottom). The specific transcription factor (TF) interacts with the enhancer to form DNA looping which delivers the enhancer bound TF to RNAPII positioned at the promoter. The DNA looping enhances transcription complex formation and activates transcription...

From the qualitative form of Fig. 3.66 one can predict certain changes in geometry and NBO composition that are promoted by strong oab-ocd interaction, and that reciprocally enhance this interaction. We shall use the example of the strong nx-(TcD interaction of NH2CH2F (see Fig. 3.64) to illustrate these changes, as summarized in Tables 3.24 (geometry) and 3.25 (NBO composition). 

In addition to containing protein-protein interaction motifs, E3-substrate specificity may be affected by post-translational modifications. In particular, phosphorylation can alter E3-substrate interactions. One example is p53 where certain phosphorylations inhibit its direct binding to Mdm2, while others indirectly enhance their association by promoting nuclear localization of p53 [104-106]. Phosphorylation also directly enhances substrate interactions, as exemplified by the Cbls, which include phospho-tyrosine binding domains (see below) [107]. 

Stabilization of a P-hairpin structure can be achieved in two ways, promoting a stable (or restricted) turn structure (as done with mimetics) or linking the two arms either chemically, or, more naturally, by hydrophobic interactions. In an approach to utilizing both methods, a D-Pro-Gly linkage was used to stabilize a left-handed turn (type I or II ) and various charged and hydrophobic residues were used to stabilize the molecule and enhance the interaction between arms. I252"254 Examples of these peptides studied in nonaqueous solution by IR, VCD and NMR spectroscopy exhibit characteristics of well-formed hairpins. 255 Alternatively, in aqueous solution, IR, VCD, and ECD results for related peptides agree with the NMR interpretation of conformations characterized as hairpins stabilized at the turn and frayed at the ends. 256 These latter results also have a qualitative match with theoretical simulations. Recently, examples of hydrophobically stabilized hairpins studied by NMR spectroscopy have avoided use of a nonnatural amino acid. 257,258 ... 

At low temperature, reduce dielectric constant and enhance electrostatic interactions between protein molecules Removes protein-bound water molecules and promotes hydrophobic interactions between protein molecules Neutralize charge of protein, which decreases protein solubility in aqueous environment... 

At least three types of proteins regulate transcription initiation by RNA polymerase specificity factors alter the specificity of RNA polymerase for a given promoter or set of promoters repressors impede access of RNA polymerase to the promoter and activators enhance the RNA polymerase-promoter interaction. 

Another method is based on the ability of some permeation enhancers to interact with intracellular proteins such as keratins inside corneocytes. The disassembly of these proteins structures within the corneocytes allows some compounds to transcel-lularly penetrate the stratum corneum. Also, some enhancers act as vehicles and cosolvents, increasing and promoting the partitioning of compounds into the stratum corneum (Table 6). 

Like replication, transcription requires separation of the duplex DNA strands and uses a polymerase to copy the template DNA strand. For transcription, the polymerase is RNA polymerase II, which binds to sequences in the regulatory region of the gene called the promoter. Promoters occur approximately 100 bases upstream (i.e., at the 5 end) from the initiation site of transcription where the first ribonucleotide unit is paired with the template (uracil pairs with adenine). Promoters are usually rich in thymine and adenine in repeating patterns and have been referred to as a TATA box. Initiation of transcription requires many protein cofactors to bind to RNA polymerase to form the active initiation complex. Other regions of DNA known as enhancers may interact with the initiation complex to stimulate or repress transcription. Regulation of transcription is the primary mechanism cells use to control gene expression. ... 

Activators bound to a distant enhancer can interact with transcription factors bound to a promoter because DNA is flexible and the intervening DNA can form a large loop. 

Regulation of eukaryotic gene transcription. Transcription of specific genes is regulated by proteins (called specific transcription factors or transactivators) that bind to gene regulatory sequences (called promoter-proximal elements, response elements, or enhancers) that activate or inhibit assembly of the basal transcription complex and RNA polymerase at the TATA box. These specific transcription factors, which may bind to DNA sequences some distance from the promoter, interact with coactivators or corepressors that bind to components of the basal transcription complex. These protein factors are said to work in trans the DNA sequences to which they bind are said to work in cis. ... 

Fig. 9-4 Promoters interact with distant enhancers via iooping, faciiitated by the mediator compiex. (A) DNA iooping around so its enhancer sequences, via activator transcription factors, interact with the compiex that forms around RNA poiymerase ii. (B) RNA poiymerase ii, iike other eukaryotic RNA poiymerases, is recruited by transcription factors which assembie step-wise at the promoter, its C terminai taii is phosphoryiated to recruit eionga-tion factors which permit it to ieave the promoter and commence transcription. The various transcription factors (TFiiA, TFiiB, etc.) are indicated by their abbreviated names, uniike FiAT which is histone acetyi transferase.

Intermolecular bonding — Since secondary bonding forces are responsible for intermolecular bonding, polymer molecules with specific groups that promote enhanced intermolecular interaction and whose structural features lead to identity periods are more crystallizable. 

---