Question

Why do acetylation and methylation not occur simultaneously on the same lysine residue on histones?

Short answer

Answer: Acetylation and methylation cannot occur simultaneously on a single lysine residue due to steric hindrance. When a lysine residue is either acetylated or methylated, the ε-amino group is involved in forming a covalent bond with the acetyl or methyl groups, leaving no available sites for the other modification to take place. Both modifications can potentially block each other, regulating the overall chromatin structure and gene expression.

Step-by-step solution

Understanding lysine residues

Lysine is an amino acid with a primary amine group (-NH2) on its side chain. When present in histones, the ε-amino group on the side chain of lysine residues can undergo various post-translational modifications, such as acetylation, methylation, and ubiquitination. These modifications play a crucial role in regulating transcription, chromatin remodeling, and DNA damage repair.

Understanding acetylation

Acetylation refers to the addition of an acetyl group (CH3CO-) onto the ε-amino group of the lysine residue. This process is catalyzed by enzymes called histone acetyltransferases (HATs), which transfer an acetyl group from acetyl-CoA to the lysine residue. Acetylation results in the neutralization of the positive charge on the lysine side chain, leading to a weaker interaction between histone proteins and negatively-charged DNA. This weakened interaction increases the accessibility of DNA and promotes transcription.

Understanding methylation

Methylation involves the addition of one, two, or three methyl groups (CH3) onto the ε-amino group of the lysine residue. This process is catalyzed by enzymes called histone methyltransferases (HMTs), which transfer methyl groups from S-adenosyl methionine (SAM) to the lysine residue. Methylation does not alter the overall positive charge of lysine, but it can impact the recruitment of other regulatory proteins. The effect of methylation on gene expression depends on the specific lysine residue and the number of added methyl groups.

Why acetylation and methylation cannot occur simultaneously

Acetylation and methylation cannot occur simultaneously on the same lysine residue due to steric hindrance. When a lysine residue is acetylated, the ε-amino group is involved in forming a covalent bond with the acetyl group, leaving no available sites for methylation to take place. Similarly, when a lysine residue is methylated, the ε-amino group is involved in forming covalent bonds with the methyl groups, preventing acetylation from occurring. Both acetylation and methylation can potentially block each other, thus regulating the overall chromatin structure and gene expression.