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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 β039 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.
Pubmed ID: 32107331
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Open, web-based platform providing bioinformatics tools and services for data intensive genomic research. Platform may be used as a service or installed locally to perform, reproduce, and share complete analyses. Galaxy automatically tracks and manages data provenance and provides support for capturing the context and intent of computational methods. Galaxy Community has created Galaxy instances in many different forms and for many different applications including Galaxy servers, cloud services that support Galaxy instances, and virtual machines and containers that can be easily deployed for your own server.The Galaxy team is a part of BX at Penn State, and the Biology and Mathematics and Computer Science departments at Emory University.Training Infrastructure as a Service (TIaaS) is a service offered by some UseGalaxy servers to specifically support training use cases.
View all literature mentionsSoftware tools for Motif Discovery and next-gen sequencing analysis. Used for analyzing ChIP-Seq, GRO-Seq, RNA-Seq, DNase-Seq, Hi-C and numerous other types of functional genomics sequencing data sets. Collection of command line programs for unix style operating systems written in Perl and C++.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
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