@article{Cristina Fugazza_Gloria Barbarani_Sudharshan Elangovan_Maria Giuseppina Marini_Serena Giolitto_Isaura Font-Monclus_Maria Franca Marongiu_Laura Manunza_John Strouboulis_Claudio Cantù_Fabio Gasparri_Silvia M.L. Barabino_Yukio Nakamura_Sergio Ottolenghi_Paolo Moi_Antonella Ellena Ronchi_2021, place={Pavia, Italy}, title={The Coup-TFII orphan nuclear receptor is an activator of the γ-globin gene}, volume={106}, url={https://haematologica.org/article/view/9675}, DOI={10.3324/haematol.2019.241224}, abstractNote={<p>The human fetal γ-globin gene is repressed in the adult stage through complex regulatory mechanisms involving transcription factors and epigenetic modifiers. Reversing γ-globin repression, or maintaining its expression by manipulating regulatory mechanisms, has become a major clinical goal in the treatment of β-hemoglobinopathies. Here, we identify the orphan nuclear receptor Coup-TFII (NR2F2/ARP-1) as an embryonic/fetal stage activator of γ-globin expression. We show that Coup-TFII is expressed in early erythropoiesis of yolk sac origin, together with embryonic/fetal globins. When overexpressed in adult cells (including peripheral blood cells from human healthy donors and β<sup>0</sup>39 thalassemic patients) Coup-TFII activates the embryonic/fetal globins genes, overcoming the repression imposed by the adult erythroid environment. Conversely, the knock-out of Coup-TFII increases the β/γ+β globin ratio. Molecular analysis indicates that Coup-TFII binds in vivo to the β-locus and contributes to its conformation. Overall, our data identify Coup-TFII as a specific activator of the γ-globin gene.</p&gt;}, number={2}, journal={Haematologica}, author={Cristina Fugazza and Gloria Barbarani and Sudharshan Elangovan and Maria Giuseppina Marini and Serena Giolitto and Isaura Font-Monclus and Maria Franca Marongiu and Laura Manunza and John Strouboulis and Claudio Cantù and Fabio Gasparri and Silvia M.L. Barabino and Yukio Nakamura and Sergio Ottolenghi and Paolo Moi and Antonella Ellena Ronchi}, year={2021}, month={Feb.}, pages={474-482} }