The histone code hypothesis predicts that the modification marks on the histone tails should provide binding sites for effector proteins. In agreement with this notion, modular protein domains that specifically recognize acetylated (bromodomain) or methylated histone tails (chromodomain) have been identified. It is possible the variations found in such proteins correlate with unique spatial arrangements present in modified histones. Already roughly 50 enzymes are known that selectively modify the histone tail thus providing the means to make a combinatorial ‘histone code’. The heterogeneity of histone modifications found in mammalian cells and the technical limitations to making homogeneous populations of selectively modified histone proteins have prevented their rigorous study. Consequently, very few proteins exhibit a strong correlation with selective interaction with a given histone modification pattern. To determine the relevance of the hypothesis, it would be useful to develop a strategy to identify proteins that bind unique combinatorial modifications of histones.
|GENE turned OFF
|STEP 1: Bromodomain protein
(GREEN) does not recognize target and therefore does not bind histone.
|STEP 2: Acetylase enzyme
(Pac-Man) comes in and acetylates histone tail. This leaves an
acetylated lysine (green ball on histone tail)
|STEP 3: Bromodomain protein
(GREEN) recognizes acetyl-histone, binds and changes structure to
initiate assembly of chromatin-remodelling complex (Blue and yellow
|GENE turned ON