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1. An Extended DNA Binding Domain of the Estrogen Receptor Alpha Directly Interacts with RNAs in Vitro

   https://doi.org/10.1021/acs.biochem.2c00536  

   Steiner, Halley R. ; Lammer, Nickolaus C. ; Batey, Robert T. ; Wuttke, Deborah S. ( October 2022 , Biochemistry)

   Estrogen receptor alpha (ERα) is a ligand-responsive transcription factor critical for sex determination and development. Recent reports challenge the canonical view of ERα function by suggesting an activity beyond binding dsDNA at estrogen-responsive promotor elements: association with RNAs in vivo. Whether these interactions are direct or indirect remains unknown, which limits the ability to understand the extent, specificity, and biological role of ERα-RNA binding. Here we demonstrate that an extended DNA-binding domain of ERα directly binds a wide range of RNAs in vitro with structural specificity. ERα binds RNAs that adopt a range of hairpin-derived structures independent of sequence, while interacting poorly with single- and double-stranded RNA. RNA affinities are only 4-fold weaker than consensus dsDNA and significantly tighter than nonconsensus dsDNA sequences. Moreover, RNA binding is competitive with DNA binding. Together, these data show that ERα utilizes an extended DNA-binding domain to achieve a high-affinity/low-specificity mode for interacting with RNA. 

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2. Relationship between maternal environment and DNA methylation patterns of estrogen receptor alpha in wild Eastern Bluebird ( Sialia sialis ) nestlings: a pilot study

   https://doi.org/10.1002/ece3.2162  

   Bentz, Alexandra B. ; Sirman, Aubrey E. ; Wada, Haruka ; Navara, Kristen J. ; Hood, Wendy R. ( June 2016 , Ecology and Evolution)

   There is mounting evidence that, across taxa, females breeding in competitive environments tend to allocate more testosterone to their offspring prenatally and these offspring typically have more aggressive and faster‐growing phenotypes. To date, no study has determined the mechanisms mediating this maternal effect's influence on offspring phenotype. However, levels of estrogen receptor alpha (ERα) gene expression are linked to differences in early growth and aggression; thus, maternal hormones may alter gene regulation, perhaps viaDNAmethylation, ofERαin offspring during prenatal development. We performed a pilot study to examine natural variation in testosterone allocation to offspring through egg yolks in wild Eastern Bluebirds (Sialia sialis) in varying breeding densities and percentDNAmethylation ofCGdinucleotides in theERαpromoter in offspring brain regions associated with growth and behavior. We hypothesized that breeding density would be positively correlated with yolk testosterone, and prenatal exposure to maternal‐derived yolk testosterone would be associated with greater offspring growth and decreasedERαpromoter methylation. Yolk testosterone concentration was positively correlated with breeding density, nestling growth rate, and percentDNAmethylation of one out of five investigated CpG sites (site 3) in the diencephalonERαpromoter, but none in the telencephalon (n = 10). PercentDNAmethylation of diencephalon CpG site 3 was positively correlated with growth rate. These data suggest a possible role for epigenetics in mediating the effects of the maternal environment on offspring phenotype. Experimentally examining this mechanism with a larger sample size in future studies may help elucidate a prominent way in which animals respond to their environment. Further, by determining the mechanisms that mediate maternal effects, we can begin to understand the potential for the heritability of these mechanisms and the impact that maternal effects are capable of producing at an evolutionary scale.

    

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3. G Protein–Coupled Estrogen Receptor Production Using an Escherichia coli Cell‐Free Expression System

   https://doi.org/10.1002/cpps.88  

   Souza, Samson A. ; Kurohara, Dane T. ; Dabalos, Chester L. ; Ng, Ho Leung ( June 2019 , Current Protocols in Protein Science)
4. Correlating nuclear morphometric patterns with estrogen receptor status in breast cancer pathologic specimens

   https://doi.org/10.1038/s41523-018-0084-4  

   Rawat, Rishi R. ; Ruderman, Daniel ; Macklin, Paul ; Rimm, David L. ; Agus, David B. ( December 2018 , npj Breast Cancer)
5. In Silico Elucidation of the Plausible Inhibitory Potential of Withaferin A of Withania Somnifera Medicinal Herb Against Breast Cancer Targeting Estrogen Receptor

   https://doi.org/10.2174/1389201021666200129121843  

   Ali, Mohammad A. ; Farah, Mohammad Abul ; Al-Anazi, Khalid M. ; Basha, Syed H. ; Bai, Fang ; Lee, Joongku ; Al-Hemaid, Fahad M.A. ; Mahmoud, Ahmed H. ; Hailan, Waleed A.Q. ( June 2020 , Current Pharmaceutical Biotechnology)

   null (Ed.)

   Background: Estrogen Receptors (ER) are members of the nuclear intracellular receptorsfamily. ER once activated by estrogen, it binds to DNA via translocating into the nucleus and regulatesthe activity of various genes. Withaferin A (WA) - an active compound of a medicinal plant Withaniasomnifera was reported to be a very effective anti-cancer agent and some of the recent studies hasdemonstrated that WA is capable of arresting the development of breast cancer via targeting estrogenreceptor. Objective: The present study is aimed at understanding the molecular level interactions of ER and Tamoxifenin comparison to Withaferin A using In-silico approaches with emphasis on Withaferin Abinding capability with ER in presence of point mutations which are causing de novo drug resistance toexisting drugs like Tamoxifen. Methods: Molecular modeling and docking studies were performed for the Tamoxifen and WithaferinA with the Estrogen receptor. Molecular docking simulations of estrogen receptor in complex withTamoxifen and Withaferin A were also performed. Results: Amino acid residues, Glu353, Arg394 and Leu387 was observed as crucial for binding andstabilizing the protein-ligand complex in case of Tamoxifen and Withaferin-A. The potential ofWithaferin A to overcome the drug resistance caused by the mutations in estrogen receptor to the existingdrugs such as Tamoxifen was demonstrated. Conclusion: In-silico analysis has elucidated the binding mode and molecular level interactions whichare expected to be of great help in further optimizing Withaferin A or design / discovery of futurebreast cancer inhibitors targeting estrogen receptor. 

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