{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:56:33Z","timestamp":1792788993108,"version":"4.5.0"},"reference-count":202,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute"},{"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 CA270067"],"award-info":[{"award-number":["R21 CA270067"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K01 CA222707"],"award-info":[{"award-number":["K01 CA222707"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R21 CA270067"],"award-info":[{"award-number":["R21 CA270067"]}],"id":[{"id":"https:\/\/ror.org\/045p44t13","id-type":"ROR","asserted-by":"publisher"}]},{"award":["K01 CA222707"],"award-info":[{"award-number":["K01 CA222707"]}],"id":[{"id":"https:\/\/ror.org\/045p44t13","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["134088-IRG-19-143-33-IRG"],"award-info":[{"award-number":["134088-IRG-19-143-33-IRG"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"award":["134088-IRG-19-143-33-IRG"],"award-info":[{"award-number":["134088-IRG-19-143-33-IRG"]}],"id":[{"id":"https:\/\/ror.org\/02e463172","id-type":"ROR","asserted-by":"publisher"}]},{"name":"UVA Comprehensive Cancer Center"},{"name":"Elsa U. Pardee Foundation","id":[{"id":"https:\/\/ror.org\/05sjnvv07","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/05sjnvv07","id-type":"ROR","asserted-by":"publisher"}]},{"name":"State funding within the UVA Comprehensive Cancer Center and UVA School of Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>PU.1 is a hematopoietic ETS-family transcription factor that serves as a master regulator of immune cell development, lineage commitment, chromatin organization, and innate immune function. PU.1 is essential for the generation and maintenance of monocytes, macrophages, dendritic cells, granulocytes, and B lymphocytes, while its repression is required for T-cell lineage commitment. As a lineage-determining transcription factor, PU.1 establishes cell identity by binding enhancer elements, recruiting chromatin remodelers, and cooperating with partner factors such as C\/EBP\u03b1, RUNX1, IRF8, and GATA factors. Tight quantitative control of PU.1 is critical, as both reduced and excessive activity can disrupt hematopoiesis and immunity. Dysregulation of PU.1 has been implicated in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), lymphoid malignancies, chronic inflammatory disorders, fibrosis, and neurodegenerative disease. Recent structural and mechanistic advances have provided insights into the structure of PU.1, DNA recognition specificity, post-transcriptional regulation, and therapeutic vulnerabilities. In this review, we summarize current knowledge of PU.1 protein structure, regulatory mechanisms, binding partners, roles in disease, and emerging strategies to therapeutically target PU.1-centered networks.<\/jats:p>","DOI":"10.3390\/biology15181657","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:01:38Z","timestamp":1789981298000},"page":"1657","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PU.1 as a Master Regulator of Immune Cell Development and Function: Structural Basis, Gene Regulatory Networks, Disease Roles, and Therapeutic Targeting"],"prefix":"10.3390","volume":"15","author":[{"given":"Mili","family":"Ramani","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Gachon University, Global Campus, Seongnam-si 13120, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3654-3747","authenticated-orcid":false,"given":"Jamie","family":"Solis","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6423-3888","authenticated-orcid":false,"given":"Daniel G.","family":"Tenen","sequence":"additional","affiliation":[{"name":"Harvard Medical School Initiative for RNA Medicine, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0956-8941","authenticated-orcid":false,"given":"Bon Q.","family":"Trinh","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA"},{"name":"Center for RNA Science and Medicine, University of Virginia, Charlottesville, VA 22908, USA"},{"name":"Molecular Genetics & Epigenetics Program, University of Virginia Comprehensive Cancer Center, Charlottesville, VA 22908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nri2024","article-title":"Transcription factors in myeloid development: Balancing differentiation with transformation","volume":"7","author":"Rosenbauer","year":"2007","journal-title":"Nat. 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