Untangling the human estrogen receptor gene structure

Abstract

Awareness of estrogen's neuroprotective and behavioral effects is broadening rapidly and has served as an incentive to investigate estrogen signaling in central nervous system disorders. The present analysis focuses on two human nuclear estrogen receptors, ER alpha and ER beta, which have been shown to play key roles in the complex integration of estrogen's genomic and non-genomic modes of action. The corresponding genes are estimated to have diverged from an ancestral ER gene over 450 million years ago and are candidate genes for a variety of brain disorders. Recent progress in the Human Genome Project has greatly aided our understanding of the molecular blueprint and provides the means for reassessing both genes' genomic organization. Analyses of multiple alternatively spliced transcripts, large untranslated sequences and neighbouring genes reveal several novel features which suggest an increasingly versatile transcriptional machinery. We outline additional exons in the genes' 5'- and 3'-untranslated regions, a new polymorphic ER alpha microsatellite and a nested gene which lend themselves to further evolutionary and functional studies.

Soyfood intake and breast cancer survival: a followup of the Shanghai Breast Cancer Study

“…ER-a and ER-b are nuclear receptor proteins that act as ligand-inducible transcription factors and mediate the effects of estrogens within breast tissue [21]. Phytoestrogens can bind to both ER-a and ER-b due to their structural similarity to estradiol.…”

Polymorphisms in genes of the steroid hormone biosynthesis and metabolism pathways and endometrial cancer risk

“…The ESR1 (GT)n repeat polymorphism has only been recently discovered and genotyped in two previous study of breast cancer patients [36,37]. Cai et al (2003) proposed that the ESR1 (GT)n repeat polymorphism may interfere with transcriptional processes as it is located in the promoter of ESR1 [36,38] and that this repeat polymorphism may affect the expression of other downstream targets by influencing transcription and/or stability of mRNA [36]. The ESR1 (TA)n repeat polymorphism has been studied in a number of cancers, including endometrial cancer [39].…”

Estrogen Receptors: Their Actions and Functional Roles in Health and Disease

“…The ERα and ERβ proteins in humans are encoded by genes spanning approximately 450 kb of chromosome 6 and 260 kb of chromosome 14, respectively, each comprised of eight coding exons interrupted by long introns [70]. The primary structure and modular organization of the two ERs are similar to the other members of the nuclear receptor family, comprising five distinguishable domains, A/B, C, D, E, and F [28] ( Figure 5.1).…”