Increase of HMGA1a protein methylation is a distinctive characteristic of leukaemic cells induced to undergo apoptosis.

HMGA1a, HMGA1b and HMGA2 are three small proteins (about 100 amino-acid residues) that constitute the family of nuclear phosphoproteins HMGA (previously known as HMGI, HMGY and HMGI-C, respectively). There is a special interest in these proteins because of their involvement in neoplastic transformation and gene expression regulation.1,2,3,4 HMGA1a and HMGA1b are derived from the same gene by alternative splicing while HMGA2 is the product of a different but related gene.5,6 The sequence of HMGA proteins contains three positively charged regions called AT-hooks, which bind DNA at the minor groove of AT-rich stretches, and a C-terminus that, on the contrary, has a high negative charge because of several glutamic acid residues.3 In a previous paper, we investigated the change of the degree of phosphorylation of HMGA1a protein during apoptosis of leukaemic cells (HL60, K562, NB4 and U937).7 We found that this protein, constitutively phosphorylated in proliferating cells, undergoes hyperphosphorylation at the early stages of apoptosis which is later followed by a dephosphorylation process linked to the chromatin remodelling that accompanies the formation of the apoptotic bodies. Here, we report a study on methylation of the HMGA1a protein that parallels the change in the degree of phosphorylation during apoptosis.