The amino acid side chains of the four histones in the nucleosome are subjected to remarkable variety of post-translation modifications such as phosphorylation, acetylation and methylation. Which one of the following post-translational marks on histone tails is usually associated with transcriptional repression?
- Acetylation of H3K9
- Methylation of H3K9
- Acetylation of H4K5
- Phosphorylation of H3S10
Rephrasing the question:
Which post-translational modification is associated with histones and transcriptional repression?
Methylation of Histone 3 at the 9th lysine (H3K9) causes transcriptional repression (option 2).
Histones are the proteins that DNA is coiled around to (a) keep it compact, and (b) regulate its expression. Post-translational modifications can be made to histones to regulate how tightly DNA is wound around them, and thus to regulate how much transcription a gene in that area undergoes. (This falls under epigenetics.)
There are 5 families of histones: H1/H5, H2A, H2B, H3, and H4. H1/H5 are known as linker histones and the remaining four are known as core histones. This is because the core histones form the body of the nucleosome (two dimers of H2A + H2B, with a tetramer of H3 + H4) around which the DNA wraps. The linker histones bind the portion of DNA where it starts to wraps around the nucleosome and the portion where it stops wrapping around the nucleosome; in effect, it ‘locks’ the structure and position of the DNA around the nucleosome.
There are a number types of modifications a histone can undergo. These usually happen at the N-terminus ‘tail’ of the histone which sticks out from the main protein body, is rich in lysine (K) and arginine (R), and is highly positively charged.
The two most important modifications are methylation and acetylation. These are used to regulate gene expression. Other types of modifications, such as phosphorylation, SUMOylation, and ubiquitination, modify histone action, localization, and degradation.
There is a shorthand to describe such modifications. This is:
Histone number + amino acid on which modification occurs + type of modification + number of such modifications
So, for instance, H3K9Me1 means that on Histone 3 (H3), on its lysine-9 residue (K9), there is a single (1) methylation (Me).
Now, what do these modifications do? First let’s look at acetylation. This is the addition of a negatively-charged acetyl group to a lysine residue, which reduces the overall positive charge of the histone. Since DNA is negatively charged, making the histone less positive (= more negative) makes the DNA bind less tightly to the histone. This ‘more free’ DNA can then be transcribed more easily; so acetylation leads to transcriptional activation.
Next we have phosphorylation of serine, threonine, or tyrosine side-chains. Phosphate groups are also negatively charged, so histone phosphorylation also results in transcriptional activation. (It also has other roles, such as in DNA repair and chromatin condensation.)
Histone methylation is the addition of one or more methyl groups to lysine or arginine. Methylation of some amino acids causes gene activation, while methylation of other residues causes repression. This is because methylation does not have a straightforward effect on the charge of the histone. The effect it has depend on how other proteins recognize the methylated vs. non-methylated histones.
Luckily, in this question, there is only one option with methylation! So, option 2, the methylation of the lysine-9 residue of histone 3 will result in transcription repression.