Final Paper On Estrogen Receptor 1 Arizona/Genetics Essay

2171 words - 9 pages

Introduction: Estrogens play a vital role in physiological processes involved in reproduction, sexual development, cardiovascular health, and bone integrity4. ESR1, a gene which encodes the estrogen-receptor alpha (ERα) is an important part of these processes. ERα is a nuclear steroid hormone receptor which acts as a transcription factor to regulate cell proliferation. It is also involved in estrogen signaling, which facilitates processes in the female reproductive system such as breast formation and ovulation. ERα is highly expressed in tissues such as the breast and ovaries, and this has been linked to carcinogenesis, or cancer formation5.
Gene Background: The ESR1 gene is located on chromosome 6 between positions 25.1 and 25.2, fixed on the 151,654,148 to 152,129,604 base pairs1.
Figure 1: ESR1 gene location- chromosome 6 between positions 25.1 and 25.21.
ESR1 is a large gene that spans 473 kb and has 8 exons. This gene is composed of three domains including an N-terminal domain also known as the AF-1 domain, a DNA-binding domain, and a C-terminal ligand-binding domain also known as the AF-2 domain. The AF-1 domain contains a ligand-independent transactivation function whereas the AF-2 domain contains a ligand-dependent transactivation function. Both the AF-1 and AF-2 domains are responsible for activating transcription. They accomplish this both in an independent fashion and also in a synergistical fashion, meaning that the overall effect is larger than the sum of individual effects4. The gene has been discovered to have 87 ornologues and some examples of these are chimpanzees, Rhesus monkeys, dogs, cows, mice, rats, chickens, zebrafish, and frogs3. ESR1 has been studied in animal models, specifically in mice in order to determine its function in certain human organs.
ERα is the transcription factor belonging to this gene and it is part of the nuclear receptor family. The nuclear receptor family is a class of proteins that play a role in sensing thyroid and steroid hormones10. There are several receptors part of this family and some examples of these include: the vitamin D receptor (PPP1R163), the thyroid receptor alpha (THRα), and the progesterone receptor (PR)10. The full length of ERα is 595 amino acids long. It contains two short isoforms: hERα-46 and hERα-36. These isoforms lack the AF-2 region of the three domains. There are 15 different transcripts of ERα and resulting from these transcripts are 47 different phenotypes1. There are several different splice variants associated with ESR1, but the full-length nature of most these variants has not been determined4. The 5’-untranslated region, or UTR has shown to differ in ERα when comparing most splice variants, but they do not differ in the coding sequence. ERα can form a heterodimer with another close receptor, ERβ. These two estrogen receptors have been shown to have very similar homology with the difference being in their N-terminal domains1. Together, they work to accomplish...

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