molecular biology - In what sense is the "histone code" a code?

Since I started learning about molecular cell biology, I have witnessed an increasing amount of attention to this thing called a "histone code." However, unlike the central dogma of molecular cell biology (i.e. DNA RNA Protein), I still feel very confused about what exactly constitutes the histone code. Is this term code being used rigorously like it is for the central dogma? That is, is there an actual code? If so, what is its alphabet (e.g. GTAC for DNA, GUAC for RNA, the amino acids for proteins)? What kind of words does it encode (e.g. codons for RNA to protein)?

If these things are not known, how do we know it's actually a code then?

Thanks!

Answer

As already mentioned by Stefan, the "histone" code is not really a universal code; it is restricted to eukaryotic systems and even then, not unambiguous. It is, at present related to two kinds of histone modifications and their correlation with the transcriptional activity at that locus:

• Methylation


• Acetylation

Other modifications such as phosphorylation and ubiquitylation also exist but they are not generally considered in this "code".

Acetylation masks the histone's positive charge and thereby loosens the chromatin (DNA wrapped around the histones), which in turn facilitates transcription. Therefore acetylation is almost always activating in the sense of gene expression.

Methylation, on the other hand has different effects. Methylation on Histone-3 at 4th lysine (H3K4) and H3K36 causes activation whereas H3K9 and H3K27 are repressive. There is also some difference between different extent of methylation i.e monomethylation, dimethylation and trimethylation. The effect of methylation is executed by proteins that have domains such as chromodomain and PHD fingers, that identify these modified histones. Sometimes the histone can carry both kinds of methylation marks H3K4me3 and H3K27me3 and these are called bivalents.

Other histones of the octameric nucleosome can also be modified. However as with other kinds of modifications that I mentioned previously they do not seem to be very common and are therefore not generally considered in this "code".