Sequence and analysis of the murine Hmgiy (Hmga1) gene locus

The HMGIY non-histone proteins play important roles as architectural transc ription factors that regulate gene transcription in mammalian cells and als o act as host-supplied cofactors. necessary for retroviral integration. The genes coding for the HMGIY proteins are protooncogenes, and their aberrant or over-expression is correlated with both neoplastic transformation and m etastatic progression in a wide variety of tumors. Here, we report the firs t complete sequence of the murine Hmgiy (a.k.a. Hmga1) gene and provide a d etailed comparison of this with the sequence and organization of the human HMGIY gene, including an analysis of its promoter region with the previousl y unreported 5' upstream region of the human gene. These analyses reveal a remarkable degree of overall sequence conservation in both the protein codi ng and promoter regions of the murine and human genes, including conservati on of the c-Myc binding site that has been demonstrated to regulate murine Hmgiy transcription (Wood et al., 2000. Mol. Cell. Biol. 20, 5490-5502). Th e promoters of both genes contain other conserved transcription factor bind ing sites that may also represent important cis-regulatory elements. Two ex ons present in the 5' untranslated region of the human gene, however, are m issing from the murine gene, suggesting that these two closely related mamm alian species regulate transcription of their Hmgiy genes in an individuali stic manner. 2001 Elsevier Science B.V. All rights reserved.