Insulators
Today I thought I could kill two birds with one stone, and study up about insulator elements, which i don’t really understand at all to be honest. So bear with me my avid readers (cough).
Right, what do I always do first in a situation like this is hit http://www.ncbi.nlm.nih.gov/
best place to start. So a quick book search and i see that apparently ‘insulators define functional domains’ and ‘maintain the independence of functional domains’. So i ask, “What does this mean?” and so our/mostly mine (as Im the only reader of this shit) journey begins.
Ok so in 1991 a group lead by Kellum and Schedl were playing around with the positional effect. Breifly the positional effect refers to a general problem in GE that when you introduce a cloned gene into a genome and intergrate it, often (depending on the mechanism used) the insertion is random. Gene expression is very dependent on the spatial positioning of the gene at any given time, such that if a gene is inserted into a heterochromatic region it will be silenced and therefore not expressed, while if it is inserted into a region of open chromatin configuration it will be expressed. Kellum et al were able to show that when the W (dominant giving red eyes) was inserted randomly into the genomes of w- drosophila variable red eye expression was observed (owing to the positional effect). When the W gene was flanked by 1-2kb insulator elements the variable expression was lost and all progeny were red eyed. Kellums group interpreted this to mean that somehow the insulator elements were able to bring about changes in the chromatin where the transgene had inserted and bring about stable expression, or in more technical terms, establish a ‘functional domain’.
Consider a situation where by we have two genes that are next door to each other. Let me introduce a bug with two genes: gene ‘go_left’ and gene ‘go_right’. Upstream of each of these genes are there respective control elements, which will turn on the expression of these genes. The signal to go left is received, and transcription begins from go_left, the bug goes left. But potentially the go_right gene could be transcribed from the go_lefts control element, and if this happens then the bug will end up in an infinate loop of go left, go right and never get where it wants to go. So god being good and great and awesome bla bla.. saw this mathematical conundrum and solved it with a stroke of genious – said ‘LET THERE BE INSULATION’ (p.s creationist’s dont belong in this blog)
Ok so back to the point im trying to make to myself: INSULATORS DEFINE FUNCTIONAL DOMAINS.
So NCBI disapointed on this topic. The article I read then went on to say that insulators do not them selfs provide insulation, but insulate by way of the proteins that they recruit. Also that it has been shown that such insulator binding proteins also bind to the nuclear matrix. From what I can gather about the nuclear matrix, I get the feeling that it is an extreamly important controler of gene regulation. One day shitwolf.. one day..
Anyway so if these proteins that are binding to insulator elements, also bind to the nuclear matrix, you can imagin that insulators may be able to physically define structural and spatial domains in the chromatin. But then the article falls flat on its face, and runs away scared. I am sent else where on my journy…