The Half Decent Pharmaceutical Chemistry Blog

Now that the major attraction of this blog, Saturday Night Synthesis, is over, I face the issue of coming up with something to make this blog worth-reading. A friend of mine has recently come up with a pretty intriguing idea: gossip.
Plainly, he believes I should as most of newspapers these days which, for example, show much more interest in Sarkozy’s love affairs rather than in his opinions on, say, illegal immigration. In fact, focusing my catchy introductions on popular topics would attract readers, so that I could eventually trap them in a labyrinth of scientific facts.

Well, let’s give it a try, by looking at one of favourite countries: France. Now, you all know Monsieur Sarko (who, if you are American, is the French president), 53, divorced from his second wife Cecilia, 50, and almost instantly turned to and got married with Italian, former super-model, Carla Bruni, 40. Can you find in your heart the force to blame him?

This switch might have inspired a French group when focusing their attention on a less glamorous switch not between models but heterochromatin proteins HP1β and HP1γ (doi:10.1038/embor.2008.1).
Despite not being as sexy as Carla Bruni, these histone modifiers are equally very interesting, as their role is far from being understood.
For many years, due to their HMTase activity (which stands for histone methyl transferase) and their huge presence at pericentromeric heterochromatin domains, they have been considered to act as pure silencers of gene expression. Recently, however, many findings has started undermining the basis of this assumption. HP1γ, for instance, has been frequently spotted at active euchromatic genes and a transcription-dependent recruitment has been proposed.

What the article mainly focuses on is the way these proteins act on HIV-1 5’ long terminal repeat, a well-known promoter of retroviruses. Interestingly, both NF-kB and protein kinase signal-transduction pathways stimulate this promoter and both phosphorylate epigenetic-regulation hot spot serine 10 on histone H3.
Obviously, I can’t (and don’t want to) tell you how these French reach their conclusions because that would mean breaking copyright rules. However, going back at the beginning story of Sarko’s love affairs, they postulate a switch between mainly transcription repressing HP1β/transcription stimulating HP1γ due to the aforementioned H3S10 phosphorylation, which they describe using the appealing expression Phospho-Switch. What this names underlines, though, is that not only is the phosphorylation the key aspect of this mechanism, but that it comprehensively overcomes the already existing tri-methylation of lysine 9 on histone H3 (to which HP1β binds), possibly altering HP1β binding site on histone 3 so much that it’s displaced and, after a brief moment while ChIP experiment shows nothing on the 5’-LTR, HP1γ is quickly recruited. Which is basically like displacing an old wife and quickly getting a younger, hotter new one, isn’t it?

In case psi*psi were reading this, happy birthday and, to already answer your question, no: there are no gels in this molecular biology affair.