HMGI/Y proteins: flexible regulators of transcription and chromatin structure

The mammalian HMGI/Y (HMGA) non-histone proteins participate in a wide vari ety of cellular processes including regulation of inducible gene transcript ion, integration of retroviruses into chromosomes and the induction of neop lastic transformation and promotion of metastatic progression of cancer cel ls. Recent advances have contributed greatly to our understanding of how th e: HMGI/Y proteins participate in the molecular mechanisms underlying these biological events. All members of the HMGI/Y family of 'high mobility grou p' proteins are characterized by the presence of multiple copies of a conse rved DNA-binding peptide motif called the 'AT hook' that preferentially bin ds to the narrow minor groove of stretches of AT-rich sequence. The mammali an HMGI/Y proteins have little, if any, secondary structure in solution but assume distinct conformations when bound to substrates such as DNA or othe r proteins. Their intrinsic flexibility allows the HMGI/Y proteins to parti cipate in specific protein-DNA and protein-protein interactions that induce both structural changes in chromatin substrates and the formation of stere ospecific complexes called 'enhanceosomes; on the promoter/enhancer regions of genes whose transcription they regulate. The formation of such regulato ry complexes is characterized by reciprocal inductions of conformational ch anges in both the HMGI/Y proteins themselves and in their interacting subst rates. It may well be that the inherent flexibility of the HMGI/Y proteins, combined with their ability to undergo reversible disordered-to-ordered st ructural transitions, has been a significant factor in the evolutionary sel ection of these proteins for their functional role(s) in cells. (C) 2001 El sevier Science B.V. All rights reserved.