Cloning, sequencing and characterization of the rat hereditary hemochromatosis promoter: comparison of the human, mouse and rat HFE promoter regions

We have cloned and sequenced 1398 bp of the rat HFE gene promoter region. T he alignment of the rat promoter HFE sequence with the HFE promoter sequenc e from human and mouse detected several highly conserved sequences present at orthologous or heterologous positions in the three species. Subsequent a nalysis of the conserved promoter sequences identified the presence of 10 n ovel transcription elements present in the promoter regions of the human, m ouse and rat HFE genes (GATA, NF-IF6, AP1, AP2, CREB, PEA3, gamma-IRE, GFII , HNF-3 beta, HFH2). Different gel retardation analyses performed with rat- liver nuclear extracts have confirmed the presence of factors binding to so me of these transcription elements. This represents the first data concerni ng the identification of potential transcriptional elements of the HFE prom oter in these three species. The expression pattern of the transcription fa ctors corresponding to the novel elements identified in the HFE promoter is consistent with the potential role of the HFE promoter in the transcriptio n regulation and function of the HFE gene. Knowledge of the identified cons erved elements in the HFE promoter from human, mouse and rat provides the b asis for subsequent in-vitro or in-vivo studies leading to identification o f the detailed mechanisms involved in the regulation of the iron metabolism and the design of potential future alternative therapies. (C) 1998 Elsevie r Science B.V. All rights reserved.