Deciphering the High Mobility Group Proteins (HMGs) Code

Abstract

HMGs are the second most abundant proteins found in the chromatin and, like histones, have been associated with nuclear processes. HMGA is subdivided into three types of proteins: HMGA1a, HMGA1b and HMGA2. The current study investigates the effect of post‐translational modifications (PTMs) of HMGA1a and their implications on different cell processes. It is believed that there might be a PTMs code or pattern that determines cellular processes similar to the histone code, yet this remains elusive. To determine the existence of the suggested code, we isolated HMGA1a by acid extraction and purified it utilizing HPLC. Our objectives include mapping the array of modifications on HMGA1a using mass spectrometry based proteomics. To date, we have currently mapped twenty eight PTMs occurring on nineteen amino acid residues. Novel PTMs were found and also residues with more than one modification suggesting that the same residue with different PTMs might act as a switch for different biological functions, similar to histones i.e. H3K9me3 versus H3K9ac. Future work includes experiments to determine the functional characterization of the novel PTMs on HMGA1a in order to correlate them to distinct biological processes.