{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:20:06Z","timestamp":1787019606002,"version":"build-2736575974"},"reference-count":41,"publisher":"American Society of Hematology","issue":"26","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,12,26]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Nuclear receptor TR4 (NR2C2) was previously shown to bind to the \u2013117 position of the \u03b3-globin gene promoters in\u00a0vitro, which overlaps the more recently described BCL11 transcription factor A (BCL11A) binding site. The role of TR4 in human \u03b3-globin gene repression has not been extensively characterized in\u00a0vivo, whereas any relationship between TR4 and BCL11A regulation through the \u03b3-globin promoters is unclear at present. We show here that TR4 and BCL11A competitively bind in\u00a0vitro to distinct, overlapping sequences, including positions overlapping \u2013117 of the \u03b3-globin promoter. We found that TR4 represses \u03b3-globin transcription and fetal hemoglobin accumulation in\u00a0vivo in a BCL11A-independent manner. Finally, examination of the chromatin occupancy of TR4 within the \u03b2-globin locus, compared with BCL11A, shows that both bind avidly to the locus control region and other sites, but only BCL11A binds to the \u03b3-globin promoters at statistically significant frequency. These data resolve an important discrepancy in the literature and, thus, clarify possible approaches to the treatment of sickle cell disease and \u03b2-thalassaemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024024599","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T16:46:43Z","timestamp":1728665203000},"page":"2762-2772","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":4,"title":["TR4 and BCL11A repress \u03b3-globin transcription via independent mechanisms"],"prefix":"10.1182","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8946-8990","authenticated-orcid":false,"given":"Yu","family":"Wang","sequence":"first","affiliation":[{"name":"1Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2810-8091","authenticated-orcid":false,"given":"Greggory","family":"Myers","sequence":"additional","affiliation":[{"name":"1Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI"},{"name":"2Division of Hematology\/Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4897-1265","authenticated-orcid":false,"given":"Lei","family":"Yu","sequence":"additional","affiliation":[{"name":"1Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI"},{"name":"2Division of Hematology\/Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0365-6278","authenticated-orcid":false,"given":"Kaiwen","family":"Deng","sequence":"additional","affiliation":[{"name":"3Department of Computational and Medical Bioinformatics, University of Michigan Medical School, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1062-6774","authenticated-orcid":false,"given":"Ginette","family":"Balbin-Cuesta","sequence":"additional","affiliation":[{"name":"2Division of Hematology\/Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6471-3171","authenticated-orcid":false,"given":"Sharon A.","family":"Singh","sequence":"additional","affiliation":[{"name":"4Division of Hematology\/Oncology, Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanfang","family":"Guan","sequence":"additional","affiliation":[{"name":"3Department of Computational and Medical Bioinformatics, University of Michigan Medical School, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2539-5953","authenticated-orcid":false,"given":"Rami","family":"Khoriaty","sequence":"additional","affiliation":[{"name":"1Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI"},{"name":"2Division of Hematology\/Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9593-1825","authenticated-orcid":false,"given":"James Douglas","family":"Engel","sequence":"additional","affiliation":[{"name":"1Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"23","key":"2024122616205015600_bib1","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1056\/NEJM199406093302303","article-title":"Mortality in sickle cell disease. 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