Characterization of the fundamental properties of the N-terminal truncation (Δ exon 1) variant of estrogen receptor α in the rat

Gene. 2015 Oct 15;571(1):117-25. doi: 10.1016/j.gene.2015.06.086. Epub 2015 Jul 4.


The estrogen receptor α (ERα) directs transactivation of target genes, and splice variants have been shown to exhibit altered activation properties. We previously documented the complicated alternative promoter usage and splicing patterns of the rat ERα gene; however, the information was restricted to a few specific organs. Therefore, we re-examined the rat mRNA profiles of ERα, including the generation of the exon 1-skipping, ERα46 transcript in a wider variety of rat organs and further characterized the fundamental functional properties of rat ERα46 variants. With the use of RT-PCR, we discovered unique distribution and splicing patterns for promoter-specific ERα isoforms, as well as the extensive expression of the Δ exon 1 variant in the rat. Similar to wild-type ERα, an immunocytochemical analysis showed a predominant localization of ERα46 proteins in the nuclei of transfected cells. Luciferase reporter assays revealed that ERα46 variants stimulated the transcriptional activity of an estrogen response element-driven promoter in response to estrogen. In addition, the variants exhibited distinct transactivation and reactivity to 4-hydroxytamoxifen in different cell types. Although the alternative splicing patterns are species-specific, the profiles of the alternative use of promoters, and the fundamental properties of the rat ERα46 variant are similar to those of human and mouse homologs. Therefore, the present study provides fundamental and useful information for further research into the regulation and functions of ERα gene variants.

Keywords: Alternative promoter usage; Alternative splicing; ERα46; ERα66; Estrogen receptor α; Splice variant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Animals
  • Cell Nucleus / metabolism
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor alpha / metabolism
  • Estrogens / pharmacology
  • Exons / genetics*
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / drug effects
  • Genetic Variation*
  • HEK293 Cells
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Microscopy, Fluorescence
  • NIH 3T3 Cells
  • Promoter Regions, Genetic / genetics
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Rats, Wistar
  • Response Elements / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / pharmacology


  • Estrogen Receptor alpha
  • Estrogens
  • Protein Isoforms
  • Tamoxifen
  • afimoxifene