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Genomic Organization of the 5′-untranslated Regions of Estrogen Receptor α Genes

The estrogen receptor α (ERα) functions as a ligand-inducible transcription factor and plays pivotal roles in various biological processes in reproductive and non-reproductive organs. Expression of the ERα gene is subject to complicated regulation. The gene has a multiple promoter system which regulates spatial and temporal expression of ERα transcripts. Furthermore, the 5'-untranslated regions (5'-UTRs) of ERα mRNAs have shown potency for post-transcriptional modulation. To elucidate the regulatory mechanisms of ERα expression, we comparatively examined the genomic organization of the 5'-regions of the ERα genes and the splicing profiles of their transcripts with distinct 5'-ends. Our analyses revealed the presence of multiple novel promoters and untranslated exons in the 5'-regions of the genes and showed that alternative promoter usage and alternative splicing generate numerous ERα transcripts with unique 5'-UTRs in species-specific manners. In this manuscript, we review recent images of human, mouse, and rat ERα gene structures and describe alternative splicing and expression patterns of their 5'-UTR isoforms. (日本医科大学医学会雑誌 2018; 14: 157―164)