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Ubiquitin-like containing PHD ring finger 1 (UHRF1) is a critical epigenetic modifier involved in various cellular processes. In this study, we demonstrated that it is highly expressed in T cell precursors of the thymus. Further, its deficiency results in significantly reduced thymocyte cellularity and thymus size in mice. Through systematic analysis based on single-cell RNA sequencing, we found that UHRF1 deficiency thwarts \u03b1\u03b2 T cell lineage development, whereas biasing \u03b3\u03b4 T lineage differentiation dampens the progression of immature single-positive cells. UHRF1 deficiency promotes the IL-17 secreting and ROR\u03b3t expression in \u03b3\u03b4 T cell, indicating a T\u03b3\u03b417 phenotype. Further, the analysis of gene-regulatory networks demonstrated that UHRF1 controls the expression of early growth response 1 (EGR1). UHRF1 interacts with DNA methyltransferase 1 (DNMT1) at the CpG promoter region of Egr1 loci and affects the nearby chromatin modifications of H3K9me3 and H3K4me3. Taken together, our results demonstrate that UHRF1 is a key factor that mediates the epigenetic regulation of EGR1 and, consequently, thymocyte fate decisions.<\/jats:p>","DOI":"10.4049\/jimmunol.1901471","type":"journal-article","created":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T19:45:17Z","timestamp":1588362317000},"page":"3248-3261","source":"Crossref","is-referenced-by-count":12,"title":["UHRF1 Controls Thymocyte Fate Decisions through the Epigenetic Regulation of EGR1 Expression"],"prefix":"10.1093","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5232-0335","authenticated-orcid":false,"given":"Yiwen","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, Guangdong 510080 ,","place":["China"]},{"name":"Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, Guangdong 510080 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Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, Guangdong 510080 ,","place":["China"]},{"name":"Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, Guangdong 510080 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junsong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, Guangdong 510080 ,","place":["China"]},{"name":"Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, Guangdong 510080 ,","place":["China"]},{"name":"Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, Guangdong 510080 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