{"entity": "publication", "iuid": "b6bf725a83764bc7a6923c1552921b4f", "timestamp": "2026-10-05T01:22:20.820Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b6bf725a83764bc7a6923c1552921b4f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b6bf725a83764bc7a6923c1552921b4f"}}, "title": "COUP-TFII regulates hemoglobin switching by activating the BCL11A-XL repressor LIN28B and directly binding \u03b4 and \u03b2 globin promoters in fetal versus adult erythroid cells.", "authors": [{"family": "Frigo", "given": "Carlotta", "initials": "C"}, {"family": "Pastori", "given": "Valentina", "initials": "V"}, {"family": "Zambanini", "given": "Gianluca", "initials": "G"}, {"family": "Fabiano", "given": "Martina", "initials": "M"}, {"family": "Ahmed", "given": "Sajeela", "initials": "S"}, {"family": "Citterio", "given": "Elisabetta", "initials": "E"}, {"family": "Cant\u00f9", "given": "Claudio", "initials": "C"}, {"family": "Ronchi", "given": "Antonella Ellena", "initials": "AE"}], "type": "journal article", "published": "2026-05-01", "journal": {"title": "Haematologica", "issn": "1592-8721", "volume": "111", "issue": "5", "pages": "1747-1758", "issn-l": "0390-6078"}, "abstract": "The reactivation of fetal globin genes is the most promising treatment for \u03b2-hemoglobinopathies. This implies the reversal of the naturally occurring hemoglobin switching. Here, we show that expression of the orphan nuclear receptor COUP-TFII in adult HUDEP2 erythroid precursor cells activates \u03b3-globin (HbF) at the expense of \u03b2-adult globin by specific occupation of the 'adult' \u03b4-\u03b2-region within the \u03b2-locus. Notably, although COUP-TFII and the main \u03b3-globin repressor BCL11A-XL share a similar DNA binding consensus and a large number of chromatin targets, including the locus control region of the \u03b2-locus itself, they bind differentially to the \u03b3 and \u03b2 promoters, eliciting an opposite transcriptional outcome. In addition, we find that COUP-TFII activates Lin28B, a known post-transcriptional repressor of BCL11A-XL. Our work identifies a molecular mechanism that could be leveraged to increase \u03b3-globin levels in patients affected by \u03b2-hemoglobinopathies.", "doi": "10.3324/haematol.2025.288485", "pmid": "41307130", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC13136808"}], "notes": [], "created": "2026-10-01T08:28:57.238Z", "modified": "2026-10-01T08:28:57.253Z"}