| First Author | Sin JH | Year | 2022 |
| Journal | J Immunol | Volume | 208 |
| Issue | 5 | Pages | 1155-1169 |
| PubMed ID | 35110421 | Mgi Jnum | J:322500 |
| Mgi Id | MGI:7257975 | Doi | 10.4049/jimmunol.2100996 |
| Citation | Sin JH, et al. (2022) ATF7ip Targets Transposable Elements for H3K9me3 Deposition to Modify CD8(+) T Cell Effector and Memory Responses. J Immunol 208(5):1155-1169 |
| abstractText | CD8(+) T cells are critical for the immune response to pathogens and tumors, and CD8(+) T cell memory protects against repeat infections. 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-specific deletion of ATF7ip have a CD8(+) T cell-intrinsic 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-Il21 intergenic region. Interestingly, ATF7ip targeted transposable elements for H3K9me3 deposition at both the IL7r locus and the Il2-Il21 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. |
