The Coup-TFII orphan nuclear receptor is an activator of the γ-globin gene

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


The human fetal γ-globin gene is repressed in adulthood 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 β039 thalassemic patients) Coup-TFII activates the embryonic/fetal globin genes, overcoming the repression imposed by the adult erythroid environment. Conversely, the knockout 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 three-dimensional conformation. Overall, our data identify Coup-TFII as a specific activator of the γ-globin gene.

Original languageEnglish
Pages (from-to)474-482
Number of pages9
Issue number2
Publication statusPublished - Feb 2021


Dive into the research topics of 'The Coup-TFII orphan nuclear receptor is an activator of the γ-globin gene'. Together they form a unique fingerprint.

Cite this