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Despite these differences, both contexts illustrate how transcription factors, chromatin regulators, and cis\u2010regulatory elements can impose disease\u2010relevant gene expression states. In \u03b2\u2010hemoglobinopathies, therapeutic reactivation of fetal hemoglobin through modulation of \u03b3\u2010globin (\n                    <jats:italic>HBG1\/2<\/jats:italic>\n                    ) regulatory pathways, most notably disruption of the erythroid\u2010specific BCL11A enhancer, has emerged as a clinically validated strategy. These advances have been facilitated in part by the HUDEP\u20102 erythroid progenitor cell line, which provides a tractable adult erythroid model for identifying fetal hemoglobin regulators, validating their function, and evaluating relevant gene editing and gene\u2010regulatory therapies. Many of the regulators implicated in \u03b3\u2010globin silencing, including BCL11A, ZBTB7A, NuRD\u2010associated proteins, DNMT1, KDM1A\/LSD1, MYB, and ATF4, also function in cancer\u2010associated transcriptional or epigenetic networks. In cancer, these factors can support oncogenic transcription, tumor suppressor repression, impaired differentiation, stress adaptation, invasion, or therapy resistance. This review summarizes discoveries enabled by HUDEP\u20102 cells in fetal hemoglobin regulation and hemoglobinopathy therapeutic development, then discusses how these mechanisms provide conceptual parallels for understanding and targeting regulatory dependencies in cancer.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70304","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T22:51:12Z","timestamp":1784242272000},"page":"2533-2566","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting transcription factors associated with hemoglobinopathies: Lessons from successful interventions and implications for cancer"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0298-2832","authenticated-orcid":false,"given":"Meigen","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Epigenetics and Molecular Carcinogenesis University 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