Help talk:Regulatory

A 'regulatory element' is often simplified into a 'promoter' but in the Registry it also includes (in addition to the RNA-polymerase binding site) the repressor/activator binding site. My suggestion is that these two (or three) regions which have well-defined characteristics and functions should be separated into distinct physical areas and carry different symbols. It might at this stage go too far into the BioBrick concept, but I believe it makes more sense making this development now than in a few years.
Additionally, I wish to suggest ;-) that the repressor binding region is depicted as --[R]-- (eg. red box with an R in it) and the activator binding region as --[A]-- (green box with an A). Further, since regulatory proteins are very important in SB, they could have separate icons as well, e.g. a red arrow --[R]--> for a repressor coding region. It would certainly add to easier understanding of composite regulatory networks. Try to explain fig. 1 in the recent Cell SB [http://www.cell.com/content/article/abstract?uid=PIIS0092867407006848 article] with currently used BioBrick icons and I am convinced you will agree with my proposals. [[http://parts.mit.edu/wiki/index.php/User:MDolinar MDolinar], July 30, 2007]

This point is well-taken, though it tends to reflect the difference between the conceptual aspects of molecular biology and the practical issues of engineering. Basic scientists define DNA binding sites in terms of their precise roles -- in this case in transcription. Thus the operator (repressor-binding site) of the lac operon consists of a specific sequence defined by footprinting. However, the promoter (RNA polymerase binding site) partially overlaps this region. The CAP (activator) site is nearby, but separate from the promoter/operator sequence. The three sites together constitute a "control region." It would be straightforward to cut out a separate piece for the CAP site, but not for the (wild-type) promoter and repressor sites. One might -- ala "refactoring" phage T7 -- design a lac promoter with no affinity for the repressor protein and an operator that could bind the lac repressor with high affinity, but not bind RNA polymerase. Then the parts would be truly independent and separable (though adding BioBrick prefixes and suffixes might compel them to be spaced too far apart for proper function). For most engineering purposes, however, the natural, overlapping system will be quite suitable and the labor of dissection can be avoided. Strictly speaking the natural promoter/repressor part is a "device," but in practice it amounts to the smallest piece of DNA that can be easily manipulated independently without refactoring. The term "regulatory element," albeit a little "fuzzy," seems suitable for such an object. As for the icons, clearly the suggested ones for repressor and activator binding sites would be useful when the sequences have only a single functional role. Overlapping functions, however, cannot be described by such a simple symbol system. Also, there is the further point that a number of regulatory proteins (e.g., the P₄ protein of B. subtilis phage φ29 and AraC from E. coli) can function as either repressors or activators depending on the gene controlled and/or cellular conditions. (See the Table of Repressor and Activator Coding Regions for more examples.) Perhaps we can use three icons, the repressor and activator ones Marko has suggested (with solid red and green coloring and inserted key letters) and then add one with stripes of red and green and the label --R/A-->. [[http://www.bu.edu/chemistry/faculty/profile/mohr.html Scott C. Mohr], July 30, 2007]