The transfer of one-carbon methyl groups to nitrogen or oxygen (N- and O-methylation, respectively) to amino acid side chains increases the hydrophobicity of the protein and can neutralize a negative amino acid charge when bound to carboxylic acids. Methylation on the tails of histone proteins, in conjunction with acetylation and phosphorylation, controls their interaction with other proteins, affects chromatin compaction and the up- or down-regulation of gene expression.