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MPECs and SLECs are epigenetically distinct; however, the epigenetic regulators required for formation of these subpopulations are mostly unknown. In this study, we performed an in vivo CRISPR screen in murine naive CD8+ T cells to identify the epigenetic regulators required for MPEC and SLEC formation, using the acute lymphocytic choriomeningitis virus Armstrong infection model. We identified the ATP-dependent chromatin remodeler CHD7 (chromodomain-helicase DNA-binding protein 7) as a positive regulator of SLEC formation, as knockout (KO) of Chd7 reduced SLECs numerically. In contrast, KO of Chd7 increased the formation of central memory T cells following pathogen clearance yet attenuated memory cell expansion following a rechallenge. These findings establish CHD7 as a novel positive regulator of SLEC and a negative regulator of central memory T cell formation.<\/jats:p>","DOI":"10.4049\/jimmunol.2400213","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T13:22:16Z","timestamp":1728307336000},"page":"1528-1541","source":"Crossref","is-referenced-by-count":3,"title":["In Vivo CRISPR Screening Reveals CHD7 as a Positive Regulator of Short-lived Effector Cells"],"prefix":"10.1093","volume":"213","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5017-774X","authenticated-orcid":false,"given":"Martin W","family":"LaFleur","sequence":"first","affiliation":[{"name":"Department of Immunology, Blavatnik Institute, Harvard Medical School , Boston, MA"},{"name":"Gene Lay Institute of Immunology and Inflammation, Brigham and Women\u2019s Hospital, Massachusetts General Hospital and Harvard Medical School , Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin 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of Immunology and Inflammation, Brigham and Women\u2019s Hospital, Massachusetts General Hospital and Harvard Medical School , Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4604-9435","authenticated-orcid":false,"given":"Lauren E","family":"Milling","sequence":"additional","affiliation":[{"name":"Department of Immunology, Blavatnik Institute, Harvard Medical School , Boston, MA"},{"name":"Gene Lay Institute of Immunology and Inflammation, Brigham and Women\u2019s Hospital, Massachusetts General Hospital and Harvard Medical School , Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Tjokrosurjo","sequence":"additional","affiliation":[{"name":"Department of Immunology, Blavatnik Institute, Harvard Medical School , Boston, MA"},{"name":"Gene Lay Institute of Immunology and Inflammation, Brigham and Women\u2019s Hospital, Massachusetts General Hospital and Harvard Medical School , Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob E","family":"Gillis","sequence":"additional","affiliation":[{"name":"Department of Immunology, Blavatnik Institute, Harvard Medical School , Boston, MA"},{"name":"Gene Lay Institute of Immunology and Inflammation, Brigham and Women\u2019s Hospital, Massachusetts General Hospital and Harvard Medical School , Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thao H","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Blavatnik Institute, Harvard Medical School , Boston, MA"},{"name":"Gene Lay Institute of Immunology and Inflammation, Brigham and Women\u2019s Hospital, Massachusetts General Hospital and Harvard Medical School , Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3869-0150","authenticated-orcid":false,"given":"Marc 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