Emerging roles of High Mobility Group A (HMGA) family members in nuclear organization

Chromatin remodeling plays a crucial role in gene expression. Chromatin architecture is governed by the interaction of a variety of proteins and transcription factors, including histones and non-histone chromatin-binding factors. Non-histone proteins, such as high mobility group-associated proteins High Mobility Group A (HMGA), are key players in this process. They do not have transcriptional activity per se but comprise flexible intrinsically disordered proteins (IDP) that interact with nucleosomes to change the compaction of chromatin at enhancers and promoters, thereby modulating the process of transcription. HMGA proteins have attained significant attention for their role in the regulation of gene expression during development, cell differentiation and in cellular senescence. Their molecular interactions are controlled by posttranslational modifications which determine nucleoprotein complex formation and function. This review highlights the role of HMGA proteins in nuclear organization, at telomeres and centromere regions and in senescence-associated heterochromatin foci and links these spatiotemporal chromatin architectural functions to the molecular domain structure of HMGA proteins in fine-tuning dynamic chromatin states.