Methylation of lysine residues on histone H3 tails regulates transcription. A recent addition to the list of known methylated histone binding modules is the plant homeodomain (PHD) finger, which is usually found in nuclear proteins with chromatin-related functions. Autoimmune regulator (AIRE) protein contains two PHD fingers and mutations in AIRE gene cause the monogenic disease autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). AIRE is expressed in thymic medullary epithelial cells where it promotes the expression of tissue-specific antigens. However the mechanism by which AIRE controls gene expression is currently unknown and the function of its domains, in particular of its PHD fingers is still elusive and controversial. In this review we discuss recent works on AIRE PHD finger(s) providing a new link between the status of histone modifications and the regulation of tissue-specific antigen expression in thymus.