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In this study, we identify the activating transcription factor 7 interacting protein (ATF7ip) as a critical regulator of CD8+ T cell immune responses. Mice with a T cell\u2013specific deletion of ATF7ip have a CD8+ T cell\u2013intrinsic enhancement of Il7r expression and Il2 expression leading to enhanced effector and memory responses. Chromatin immunoprecipitation sequencing studies identified ATF7ip as a repressor of Il7r and Il2 gene expression through the deposition of the repressive histone mark H3K9me3 at the Il7r gene and Il2\u2013Il21 intergenic region. Interestingly, ATF7ip targeted transposable elements for H3K9me3 deposition at both the IL7r locus and the Il2\u2013Il21 intergenic region, indicating that ATF7ip silencing of transposable elements is important for regulating CD8+ T cell function. These results demonstrate a new epigenetic pathway by which IL-7R and IL-2 production are constrained in CD8+ T cells, and this may open up new avenues for modulating their production.<\/jats:p>","DOI":"10.4049\/jimmunol.2100996","type":"journal-article","created":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T16:15:15Z","timestamp":1643818515000},"page":"1155-1169","source":"Crossref","is-referenced-by-count":9,"title":["ATF7ip Targets Transposable Elements for H3K9me3 Deposition to Modify CD8+ T Cell Effector and Memory Responses"],"prefix":"10.1093","volume":"208","author":[{"given":"Jun Hyung","family":"Sin","sequence":"first","affiliation":[{"name":"Division of Pediatric Rheumatology, University of California San Francisco , San Francisco, CA"},{"name":"Department of Pediatrics, University of California San Francisco , San Francisco, CA"},{"name":"Biomedical Sciences Graduate Program, University of California , San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujit","family":"Kashyap","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology, University of California San Francisco , San Francisco, CA"},{"name":"Department of Pediatrics, University of California San Francisco , San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4137-0297","authenticated-orcid":false,"given":"Dante","family":"Acenas","sequence":"additional","affiliation":[{"name":"Diabetes Center, University of California , San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica T","family":"Cortez","sequence":"additional","affiliation":[{"name":"Diabetes Center, University of California , San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1762-1677","authenticated-orcid":false,"given":"James","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of California , San Francisco, San Francisco, CA"},{"name":"Department of Medicine, University of California San Francisco , San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2734-5776","authenticated-orcid":false,"given":"Alexander","family":"Marson","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Graduate Program, University of California , San Francisco, CA"},{"name":"Diabetes Center, University of California , San Francisco, San Francisco, CA"},{"name":"J. 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